MONDO:0014658

[PMID:10377013] [SUPPORT] Other unusual bone deformities, such as femoral bowing with reverse (i.e., posterior apex) tibial and fibular bowing and "ram's horn" bowing of the clavicle, are also seen in some patients. --- Explanation: The phenotypic analysis reports fibular bowing in SADDAN.


MONDO:0014658

[PMID:10053006] [INDIRECT EVIDENCE] [SUPPORT] Transient transfection studies with FGFR3 mutant constructs show that the Lys650Met mutation causes a dramatic increase in constitutive receptor kinase activity, approximately three times greater than that observed with the Lys650Glu mutation. --- Explanation: Functional studies show Lys650Met increases constitutive FGFR3 kinase activity.


MONDO:0014658


MONDO:0014658

[PMID:10377013] [INDIRECT EVIDENCE] [SUPPORT] The FGFR3 Lys650Met mutation results in severe disturbances in endochondral bone growth that approach and overlap those observed in thanatophoric dysplasia, type I. --- Explanation: The abstract links Lys650Met to severe disturbances in endochondral bone growth.


MAXO:0000058

[PMID:38993719] [SUPPORT] We administered GH therapy for a markedly short stature. --- Explanation: Case report documents growth hormone therapy in a SADDAN patient with marked short stature.


hgnc:3690

[PMID:24352917] [SUPPORT] The disorder is the result of a single missense mutation at codon 650 (p.Lys650Met) in the fibroblast growth factor receptor 3 gene (FGFR3). --- Explanation: The abstract identifies p.Lys650Met in FGFR3 as the causal mutation.


MONDO:0007733

[PMID:34576017] [SUPPORT] SHH mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. --- Explanation: Establishes holoprosencephaly as the cardinal feature of SHH mutations.


MONDO:0007733


MONDO:0007733

[PMID:11471164] [SUPPORT] A new missense mutation in SHH (I111F), segregating in one SMMCI family, was identified. --- Explanation: Identifies an SHH mutation specific to the SMMCI phenotype, establishing SMMCI as part of the HPE spectrum.

[PMID:15103725] [SUPPORT] Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly. It is usually considered as a minor manifestation of holoprosencephaly (HPE). --- Explanation: Confirms SMMCI as a microform of HPE with novel SHH mutation.


MONDO:0007733

[PMID:20850526] [SUPPORT] we propose that holoprosencephaly and coloboma can represent mild and severe aspects of single phenotypic spectrum resulting from aberrant forebrain development. --- Explanation: Establishes coloboma/microphthalmia as part of the HPE spectrum via shared SHH signaling mechanisms.


MONDO:0007733

[PMID:29761634] [SUPPORT] In addition to the systemic consequences of pituitary dysfunction (as a direct result of brain midline defects), here we describe a number of extracephalic findings of NCNS-HPE affecting various organ systems. --- Explanation: Pituitary dysfunction is directly linked to brain midline defects in nonsyndromic HPE.


MONDO:0007733

[PMID:11471164] [SUPPORT] These anomalies include short stature, pituitary insufficiency, microcephaly, choanal atresia, midnasal stenosis, and congenital nasal pyriform aperture stenosis. --- Explanation: Choanal atresia is documented as an associated anomaly in SMMCI patients.


MONDO:0007733

[PMID:20850526] [INDIRECT EVIDENCE] [SUPPORT] It is clear that Sonic hedgehog (Shh) signaling regulates both forebrain and eye development, with defects in Shh, or components of the Shh signaling cascade leading to the generation of both birth defects. --- Explanation: Directly establishes SHH as the morphogen governing forebrain patterning, with signaling defects causing HPE.

[PMID:20850526] [INDIRECT EVIDENCE] [SUPPORT] Holoprosencephaly, the most common forebrain defect, occurs when the cerebral hemispheres fail to separate and is typically associated with mispatterning of embryonic midline tissue. --- Explanation: Links midline tissue mispatterning to hemispheric non-separation via disrupted SHH signaling.


hgnc:10848

[PMID:32939873] [SUPPORT] Genetic variation in the highly conserved Sonic Hedgehog (SHH) gene is one of the most common genetic causes for the malformations of the brain and face in humans described as the holoprosencephaly clinical spectrum. --- Explanation: Zebrafish functional analysis of 104 SHH variants establishes loss-of-function as the disease mechanism for HPE spectrum.

[PMID:34576017] [SUPPORT] SHH mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. --- Explanation: Establishes SHH as the first known genetic cause of HPE and notes the wide variability in phenotype even with the same mutation.


MONDO:0044315

[PMID:32499606] [SUPPORT] We found 18 (2.3%) different rare damaging SMAD6 variants, with the highest prevalence in metopic synostosis (5.8%) --- Explanation: This directly supports metopic synostosis as the most characteristic cranial presentation.


MONDO:0044315

[PMID:27606499] [PARTIAL] Thirteen probands (7%) had damaging de novo or rare transmitted mutations in SMAD6, an inhibitor of BMP - induced osteoblast differentiation (p<10-20). --- Explanation: This partially supports sagittal craniosynostosis as part of the broader SMAD6-associated midline craniosynostosis cohort, rather than establishing sagittal-specific enrichment on its own.


MONDO:0044315

[PMID:27606499] [PARTIAL] Premature fusion of the cranial sutures (craniosynostosis), affecting 1 in 2000 newborns, is treated surgically in infancy to prevent adverse neurologic outcomes. --- Explanation: This partially supports neurologically consequential skull-growth restriction as a downstream effect of early suture fusion.


hgnc:6772

[PMID:27606499] [SUPPORT] Thirteen probands (7%) had damaging de novo or rare transmitted mutations in SMAD6, an inhibitor of BMP - induced osteoblast differentiation (p<10-20). --- Explanation: This establishes SMAD6 as a recurrent causative gene in midline craniosynostosis.

[PMID:32499606] [SUPPORT] Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. --- Explanation: This larger cohort confirms the same gene-disease relationship across a broader craniosynostosis case series.


MONDO:0044315

[PMID:27606499] [SUPPORT] SMAD6 mutations nonetheless showed striking incomplete penetrance (<60%). --- Explanation: This directly supports reduced penetrance in SMAD6-related midline craniosynostosis.

[PMID:32499606] [SUPPORT] Combined with eight additional variants, ≥20/26 were transmitted from an unaffected parent but rs1884302 genotype did not predict phenotype. --- Explanation: This provides direct evidence for dominant transmission with unaffected carriers and variable expression.


MONDO:0958189

[PMID:25403219] [SUPPORT] We found a < 2% risk in PTCH1 mutation-positive individuals, with a risk up to 20× higher in SUFU mutation-positive individuals. --- Explanation: Quantifies major relative medulloblastoma risk increase in SUFU carriers.

[PMID:29186568] [SUPPORT] Twenty-two patients from 17 families were identified with medulloblastoma and a germline SUFU mutation (median age at diagnosis: 16.5 mo). --- Explanation: Supports very early-onset medulloblastoma in SUFU-related disease.

[PMID:35768194] [SUPPORT] The cumulative risk of an MB, gonadal tumour, BCC and meningioma at age 50 years was: 13.3% (95% CI 6 to 20.1), 4.6% (95% CI 0 to 9.7), 28.5% (95% CI 13.4 to 40.9) and 5.2% (95% CI 0 to 12), respectively. --- Explanation: Provides quantitative penetrance estimates for medulloblastoma and other tumors in SUFU carriers.


MONDO:0958189

[PMID:28596197] [SUPPORT] Patients with SUFU pathogenic variants were significantly more likely than those with PTCH1 pathogenic variants to develop a medulloblastoma (p=0.009), a meningioma (p=0.02) or an ovarian fibroma (p=0.015), but were less likely to develop a jaw cyst (p=0.0004). --- Explanation: Supports SUFU-enriched meningioma risk relative to PTCH1 carriers.


MONDO:0958189

[PMID:28596197] [SUPPORT] Patients with SUFU pathogenic variants were significantly more likely than those with PTCH1 pathogenic variants to develop a medulloblastoma (p=0.009), a meningioma (p=0.02) or an ovarian fibroma (p=0.015), but were less likely to develop a jaw cyst (p=0.0004). --- Explanation: Supports increased ovarian fibroma frequency in SUFU disease.


MONDO:0958189

[PMID:29186568] [SUPPORT] The clinical spectrum differs between SUFU and PTCH1 mutation carriers, and BCC incidence is much lower in SUFU mutation carriers. --- Explanation: Supports lower relative BCC burden in SUFU-associated syndrome.


MONDO:0958189

[PMID:25403219] [SUPPORT] All three SUFU-positive families fulfilled diagnostic criteria for Gorlin syndrome, although none had odontogenic jaw keratocysts. --- Explanation: Supports reduced jaw-cyst burden in SUFU-positive families.


MONDO:0958189

[PMID:25403219] [INDIRECT EVIDENCE] [SUPPORT] We demonstrate convincing evidence that SUFU mutations can cause classical Gorlin syndrome. --- Explanation: Establishes SUFU as a direct causal locus for the syndrome.

[PMID:29186568] [INDIRECT EVIDENCE] [SUPPORT] Germline SUFU mutations strongly predispose to medulloblastoma in the first years of life, with worse prognosis than usually observed for SHH medulloblastoma. --- Explanation: Supports high-risk early-childhood tumor predisposition in SUFU carriers.


MONDO:0958189


MAXO:0000058

[PMID:29186568] [SUPPORT] Despite treatment with surgery and chemotherapy, to avoid radiotherapy in all patients except one, the outcome was worse than expected for SHH medulloblastoma, due to the high incidence of local relapses (8/22 patients) and second malignancies (n = 6 in 4/22 patients). --- Explanation: Documents real-world treatment strategy and outcomes in SUFU-associated medulloblastoma.


MAXO:0000079

[PMID:29186568] [SUPPORT] Mutations were inherited in 79% of patients, and 34 additional SUFU mutation carriers were identified within 14 families. --- Explanation: Supports counseling and family-based cascade testing in SUFU-associated disease.


HGNC.SYMBOL:SUFU

[PMID:25403219] [SUPPORT] We demonstrate convincing evidence that SUFU mutations can cause classical Gorlin syndrome. --- Explanation: Supports SUFU as the primary causal gene in basal cell nevus syndrome 2.


MONDO:0011449

[PMID:37713976] [SUPPORT] Early childhood development was delayed with achievement of some milestones followed by a developmental plateau in late childhood. --- Explanation: Case series demonstrates cognitive/developmental impairment as core feature of Salla disease progression.


MONDO:0011449

[PMID:37713976] [SUPPORT] Disease onset occurred within the first six months of life in both patients. Early childhood development was delayed --- Explanation: Longitudinal study confirms disease onset in early infancy with delayed developmental milestones.


MONDO:0011449

[PMID:34667062] [PARTIAL] Nonimmune hydrops fetalis, the excessive accumulation of serous fluid in the subcutaneous tissues and serous cavities of the fetus, has many possible etiologies, providing a diagnostic challenge for the physician. Lysosomal storage diseases have been reported in up to 5%-16% of nonimmune hydrops fetalis pregnancies. Infantile free sialic acid storage disease (ISSD) (OMIM #269920) is a severe form of autosomal recessive sialic acid storage disease. --- Explanation: Case report demonstrates prenatal hydrops as a presenting feature of infantile-onset FSASD, with fetal hydrops detected at 24 weeks gestation.


MONDO:0011449

[PMID:37713976] [NO_EVIDENCE] Disease onset occurred within the first six months of life --- Explanation: Case series indicates early infancy as period of disease onset with motor involvement.


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [NO_EVIDENCE] Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease --- Explanation: Ataxia is a characteristic neurological manifestation of FSASD.


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [NO_EVIDENCE] Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease --- Explanation: Nystagmus is a reported neurological sign in FSASD.


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [NO_EVIDENCE] Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease --- Explanation: Muscle spasticity is a manifestation of Salla disease neurological involvement.


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [NO_EVIDENCE] Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease --- Explanation: Corpus callosum hypoplasia is a characteristic neuroimaging finding in FSASD.


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [NO_EVIDENCE] Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease --- Explanation: White matter hypomyelination is a characteristic neuroimaging feature in FSASD.


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [NO_EVIDENCE] Lysosomal free sialic acid storage disorder (FSASD) is a rare neurodegenerative disease --- Explanation: Progressive cerebellar atrophy is observed in FSASD patients on MRI.


MONDO:0011449

[PMID:35796883] [SUPPORT] Psychiatric symptoms were frequently associated with SD (10/24, 42%), and two patients were described as developing psychosis as adolescents. --- Explanation: Systematic review of 24 Salla disease patients identified psychosis as a previously unreported psychiatric manifestation, occurring in 2 of the 24 patients during adolescence.


MONDO:0011449

[PMID:35796883] [SUPPORT] Other psychiatric factors associated with SD were sleeping disorders (8/24, 32%) --- Explanation: Systematic cohort analysis of 24 Salla disease patients found sleep disorders in 32% of the population, making it a common neuropsychiatric comorbidity.


MONDO:0011449

[PMID:35796883] [SUPPORT] aggressive behaviour disorders or restlessness (6/24, 25%) --- Explanation: Cohort study of 24 Salla disease patients identified aggressive behavior and restlessness in 25% of individuals, demonstrating frequent behavioral manifestations.


MONDO:0011449

[DOI:10.1126/sciadv.ade8346] [INDIRECT EVIDENCE] [PARTIAL] Our analysis reveals two unique features in Sialin: (i) The H+ coupling/sensing requires two highly conserved Glu residues (E171 and E175) instead of one --- Explanation: 2023 Science Advances cryo-EM structure and functional assays demonstrate molecular mechanism of sialin transport and mutation effects.

[PMID:39742826] [INDIRECT EVIDENCE] [SUPPORT] Functional studies, including SLC17A5 knockout cells and transient transfections of mutated SLC17A5 demonstrated pathogenicity of the identified variants. --- Explanation: 2025 study demonstrates pathogenicity of SLC17A5 variants including tissue-specific mosaic mutations causing atypical FSASD presentations.


MONDO:0011449

[PMID:39991440] [INDIRECT EVIDENCE] [SUPPORT] In CSF, total GSLs, GM1a, GM3, GD3, GD1a, and GD1b were significantly elevated compared to comparison samples. These results reveal dysregulated GSL metabolism and suggest the potential of gangliosides as biomarkers. --- Explanation: Study of CSF and plasma in FSASD patients demonstrates dysregulated GSL metabolism with elevated gangliosides, supporting alterations in pathogenesis.


MONDO:0011449


MONDO:0011449

[DOI:10.1038/s41598-025-12682-4] [INDIRECT EVIDENCE] [SUPPORT] Oligodendroglia in FSASD pathogenesis is established, the roles of other neural cell types remain elusive. --- Explanation: iPSC disease modeling confirms oligodendroglial involvement and differential cell-type vulnerability in FSASD.


MONDO:0011449

[PMID:37713976] [INDIRECT EVIDENCE] [PARTIAL] Disease onset occurred within the first six months of life in both patients. Early childhood development was delayed with achievement of some milestones followed by a developmental plateau in late childhood. After this, both patients began a slow and progressive neurological regression in adolescence. --- Explanation: Longitudinal study documents progressive neurodegeneration from infancy through adolescence in intermediate-severe Salla disease.


hgnc:10933

[PMID:37727271] [PARTIAL] Free sialic acid storage disorders (FSASDs) result from pathogenic variations in the SLC17A5 gene, which encodes the lysosomal transmembrane protein sialin. --- Explanation: Studies of patient-derived cells demonstrate SLC17A5 biallelic mutations as causative for FSASD including Salla disease.

[PMID:34667062] [SUPPORT] SLC17A5 gene sequencing was initiated with no sequence variants identified; however, the assay failed to amplify exons 8 and 9, prompting an exon-level copy-number analysis that revealed a novel homozygous deletion of exons 8 and 9, inherited from heterozygous carrier parents. --- Explanation: Case report documents a novel homozygous deletion of SLC17A5 exons 8-9 causing infantile-onset FSASD with prenatal hydrops, demonstrating the spectrum of SLC17A5 pathogenic variants extends beyond point mutations to exonic deletions.


MONDO:0011449

[PMID:40529477] [SUPPORT] Individuals with FSASD exhibited significantly higher levels of free Neu5Ac compared to their unaffected biological parents (36-fold) --- Explanation: Free sialic acid accumulation is the pathognomonic biochemical feature and a diagnostic biomarker in FSASD.

[PMID:24993898] [SUPPORT] We describe here a 34 months child, practically asymptomatic which presented with high levels of free sialic acid in urine by biochemical detection in second-tier tests newborn screening --- Explanation: Newborn screening case report demonstrates early detection of elevated urinary free sialic acid as a diagnostic marker, enabling early identification of asymptomatic FSASD before clinical manifestations.

[PMID:29875421] [SUPPORT] The biochemical phenotype clearly predicted the disease course: patients with a urinary free sialic acid excretion below 6.37-fold or an intracellular free sialic acid storage in fibroblasts below 7.37-fold of the mean of normal survived longer than patients with biochemical values above these thresholds. --- Explanation: Large cross-sectional study of 116 FSASD cases demonstrates that biochemical biomarker levels (urinary and intracellular free sialic acid) are strong predictors of disease progression and survival, with thresholds of 6.37-fold (urine) and 7.37-fold (fibroblasts) distinguishing slower and faster disease courses.


MONDO:0019338

[PMID:31485575] [PARTIAL] Although intrathoracic involvement is the hallmark of the disease, present in over 90% of patients, sarcoidosis can affect virtually any organ. --- Explanation: This Mayo Clinic review strongly supports intrathoracic involvement as the dominant manifestation of sarcoidosis, but only indirectly supports mediastinal lymphadenopathy specifically.


MONDO:0019338

[PMID:38227868] [SUPPORT] Ongoing dyspnea and dry cough in a young to middle-aged adult should increase the suspicion for sarcoidosis. --- Explanation: This 2024 American Family Physician review identifies dyspnea as a key presenting symptom that should raise suspicion for sarcoidosis.


MONDO:0019338

[PMID:38227868] [SUPPORT] Ongoing dyspnea and dry cough in a young to middle-aged adult should increase the suspicion for sarcoidosis. --- Explanation: Dry cough is identified as a hallmark symptom that should raise clinical suspicion for sarcoidosis in younger adults.


MONDO:0019338

[PMID:38227868] [PARTIAL] Patients with sarcoidosis can exhibit constitutional symptoms such as fever, unintentional weight loss, and fatigue. --- Explanation: This review supports fatigue as a recognized constitutional symptom in sarcoidosis, but the wording is not strong enough on its own to justify a VERY_FREQUENT frequency assignment.


MONDO:0019338

[PMID:39082153] [SUPPORT] Löfgren syndrome (LS) is a sarcoidosis subtype characterised by an acute disease course, bilateral hilar lymphadenopathy (BHL), erythema nodosum (EN), and ankle arthritis. --- Explanation: This review of Lofgren syndrome directly supports erythema nodosum as a recognized acute cutaneous manifestation of sarcoidosis.


MONDO:0019338

[PMID:33173272] [SUPPORT] Uveitis was the most common ocular manifestation. --- Explanation: This retrospective series directly supports uveitis as a common ocular manifestation among patients with ocular sarcoidosis.


MONDO:0019338

[PMID:35011621] [INDIRECT EVIDENCE] [PARTIAL] Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas --- Explanation: This review confirms the characteristic non-caseating granuloma formation in sarcoidosis.


MONDO:0019338


MONDO:0019338

[PMID:24882950] [INDIRECT EVIDENCE] [SUPPORT] The proportion of Th17 cells positive for IFN-gamma was greater in sarcoidosis than controls (median 72.4% versus 31%, P = 0.0005) and increased with radiologic stage (N = 23, rho = 0.45, and P = 0.03). --- Explanation: This study directly supports enrichment of IFN-gamma-positive Th17 cells and a dysregulated effector T-cell compartment in sarcoidosis.

[PMID:26376720] [INDIRECT EVIDENCE] [SUPPORT] In untreated patients with active pulmonary sarcoidosis, Tregs show impaired survival and enhanced apoptotic susceptibility towards CD95L. Increased apoptosis likely contributes to the insufficient immunosuppressive function of sarcoidosis Tregs. --- Explanation: This study directly supports impaired regulatory T-cell survival and function as a contributor to ongoing sarcoid inflammation.


MAXO:0000640

[PMID:31485575] [SUPPORT] Glucocorticoids are the cornerstone of treatment of sarcoidosis even though evidence from randomized controlled studies is lacking. --- Explanation: This Mayo Clinic review establishes glucocorticoids as the cornerstone of sarcoidosis treatment.

[PMID:38227868] [SUPPORT] Corticosteroids are the initial treatment for active disease, with refractory cases often requiring immunosuppressive or biologic therapies. --- Explanation: This 2024 review confirms corticosteroids as first-line initial treatment for active sarcoidosis.


MAXO:0000058

[PMID:41095908] [SUPPORT] Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. --- Explanation: This evidence-based review directly supports methotrexate as a standard second-line steroid-sparing therapy in pulmonary sarcoidosis.


CHEBI:44185

[PMID:41095908] [INDIRECT EVIDENCE] [SUPPORT] Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. --- Explanation: This evidence-based review directly supports methotrexate as a standard second-line steroid-sparing therapy in pulmonary sarcoidosis.


MAXO:0000058

[PMID:41095908] [SUPPORT] For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. --- Explanation: This evidence-based review directly supports anti-TNF therapy, especially infliximab, as an option for refractory sarcoidosis.


HGNC.SYMBOL:HLA-DRB1 Variants

[PMID:25506722] [SUPPORT] This study has identified DRB1*03:01 and *03:02 as novel alleles associated with disease susceptibility and course in African Americans. --- Explanation: This large genetic association study directly supports HLA-DRB1 variation as a determinant of sarcoidosis susceptibility and clinical course.


HGNC.SYMBOL:BTNL2 Variants

[PMID:21410903] [SUPPORT] The BTNL2 A allele variant occurs with a high frequency in Danish patients with sarcoidosis and the AA genotype is associated with a ~threefold higher risk of sarcoidosis than the GG genotype. --- Explanation: This case-control study directly supports BTNL2 variation as a sarcoidosis susceptibility factor.


MONDO:0010922

[PMID:31217029] [SUPPORT] Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. --- Explanation: Painful muscle spasms are listed as one of the cardinal symptoms in this systematic review of 64 cases.

[PMID:36749015] [SUPPORT] All cases had painful muscular spasms and alopecia. --- Explanation: Independent 77-case review confirms painful spasms as a universal phenotype.

[PMID:9804090] [SUPPORT] Satoyoshi syndrome consists of painful intermittent muscle spasms, alopecia and diarrhea. --- Explanation: Adult-onset review independently confirms painful intermittent spasms as a core phenotype.


MONDO:0010922

[PMID:36749015] [SUPPORT] All cases had painful muscular spasms and alopecia. --- Explanation: The largest systematic review (77 cases) reports alopecia as universal in Satoyoshi syndrome.

[PMID:31217029] [SUPPORT] Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. --- Explanation: Independent systematic review (64 cases) also identifies alopecia as a core syndrome feature.


MONDO:0010922

[PMID:36930111] [SUPPORT] At the age of 7 years, she developed generalized hair loss and painful spasms and was diagnosed with Satoyoshi syndrome. --- Explanation: Case report documents generalized hair loss as a presenting feature of Satoyoshi syndrome.

[PMID:28940615] [SUPPORT] We report an 11-year-old girl with Satoyoshi syndrome who presented to the dermatology department for treatment of alopecia universalis. --- Explanation: Case report directly documents alopecia universalis as a presenting phenotype.


MONDO:0010922

[PMID:32429959] [SUPPORT] Chronic diarrhea was the main digestive symptom (92.3%). --- Explanation: Systematic review identifies chronic diarrhea as the predominant GI symptom in 92.3% of cases with gastrointestinal manifestations.

[PMID:36749015] [SUPPORT] Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. --- Explanation: Broader case synthesis also classifies diarrhoea as a frequent Satoyoshi manifestation.

[PMID:28267828] [SUPPORT] Thereafter, she developed chronic diarrhea, amenorrhea, and skeletal deformities. --- Explanation: Case history report independently documents chronic diarrhea among multisystem Satoyoshi manifestations.


MONDO:0010922

[PMID:32429959] [SUPPORT] The D-xylose test was positive in 10 out of 12 patients, and 9 out of 13 cases showed a flattened oral glucose tolerance test suggesting carbohydrate malabsorption. --- Explanation: Objective malabsorption testing demonstrates carbohydrate malabsorption in the majority of tested patients.

[PMID:36749015] [SUPPORT] Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. --- Explanation: Independent systematic review evidence confirms malabsorption as a frequent manifestation.


MONDO:0010922

[PMID:36749015] [SUPPORT] Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. --- Explanation: Systematic review of 77 cases identifies amenorrhoea as one of the frequent manifestations of Satoyoshi syndrome.

[PMID:15069249] [SUPPORT] Satoyoshi syndrome (Komuragaeri disease) is a rare disorder of presumed autoimmune etiology, characterized by painful muscle spasms, alopecia, diarrhea, endocrinopathy with amenorrhoea and secondary skeletal abnormalities. --- Explanation: Independent case report abstract explicitly includes amenorrhoea in the characteristic syndrome phenotype.

[PMID:28267828] [SUPPORT] Thereafter, she developed chronic diarrhea, amenorrhea, and skeletal deformities. --- Explanation: Additional case evidence directly supports amenorrhea in Satoyoshi syndrome.


MONDO:0010922

[PMID:32429959] [SUPPORT] Chronic diarrhea may be severe and result in malnutrition, anemia, growth retardation, cachexia, disability and even death. --- Explanation: Growth retardation is listed as a consequence of severe chronic diarrhea and malabsorption in Satoyoshi syndrome.

[PMID:36749015] [SUPPORT] Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. --- Explanation: Systematic review independently confirms growth retardation as a frequent manifestation.


MONDO:0010922

[PMID:31217029] [SUPPORT] Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. --- Explanation: Skeletal abnormalities are listed as one of the main symptoms in this systematic review of 64 cases.

[PMID:15069249] [SUPPORT] Satoyoshi syndrome (Komuragaeri disease) is a rare disorder of presumed autoimmune etiology, characterized by painful muscle spasms, alopecia, diarrhea, endocrinopathy with amenorrhoea and secondary skeletal abnormalities. --- Explanation: Independent case literature explicitly reports secondary skeletal abnormalities as part of the syndrome.

[PMID:28267828] [SUPPORT] Thereafter, she developed chronic diarrhea, amenorrhea, and skeletal deformities. --- Explanation: Independent case evidence supports skeletal deformities as part of the phenotype spectrum.

[PMID:12039433] [SUPPORT] The syndrome consists of the following clinical features: (1) painful, intermittent muscle spasms; (2) alopecia; (3) diarrhea; and (4) skeletal abnormalities in cases of juvenile onset. --- Explanation: This report explicitly lists skeletal abnormalities as a recognized feature in juvenile-onset Satoyoshi syndrome.


MONDO:0010922

[PMID:36930111] [SUPPORT] Unilateral granulomatous pan-uveitis and impending CRVO were observed in this patient. Several cases of Satoyoshi syndrome complicated by various autoimmune or immunological disorders have been reported. However, to the best of our knowledge, no reports of Satoyoshi syndrome presenting with uveitis or CRVO have been published. Physicians should consider uveitis as a complication of Satoyoshi syndrome. --- Explanation: First reported case of uveitis in Satoyoshi syndrome, expanding the known organ spectrum of the disease and supporting systemic autoimmune pathogenesis.


MONDO:0010922

[PMID:32429959] [SUPPORT] Other symptoms such as abdominal pain (15.4%), nausea (7.7%) and vomiting (7.7%), were less frequent. --- Explanation: Abdominal pain reported in 15.4% of cases with gastrointestinal involvement.


MONDO:0010922

[PMID:32429959] [INDIRECT EVIDENCE] [SUPPORT] Antinuclear antibodies were detected in 8 out of 16 cases. Antibodies to stomach or duodenum tissue lysates were also detected by Western blot. --- Explanation: Detection of ANA and additional tissue-reactive antibodies supports systemic autoimmunity as an upstream disease event.

[PMID:36749015] [INDIRECT EVIDENCE] [SUPPORT] Autoantibody determinations were performed in 39 patients, of which 27 had positive results. The most frequently detected autoantibodies were ANAs. --- Explanation: This broader systematic review confirms frequent autoantibody positivity and ANA predominance, reinforcing systemic autoimmune activation.

[PMID:28940615] [INDIRECT EVIDENCE] [SUPPORT] It is a rare multisystem disorder of presumed autoimmune etiology that is characterized by alopecia, intermittent painful muscle spasms, diarrhea, and antinuclear antibody positivity. --- Explanation: Independent case-report abstract supports autoimmune etiology and ANA positivity in Satoyoshi syndrome.


MONDO:0010922


MONDO:0010922

[PMID:31217029] [INDIRECT EVIDENCE] [SUPPORT] Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. --- Explanation: Systematic review of 64 cases confirms painful muscle spasms as a universal feature, with autoimmune basis presumed but specific neuromuscular mechanism not yet resolved.

[PMID:16972238] [INDIRECT EVIDENCE] [SUPPORT] These findings point to hyperactivity or a disinhibition at the alpha motor neuron level, originating probably at that level, although a central origin cannot be excluded. --- Explanation: Electrophysiologic data support alpha motor neuron hyperexcitability as a proximal mechanism for painful involuntary contractions.

[PMID:16972238] [INDIRECT EVIDENCE] [SUPPORT] During the involuntary contractions, HD-sEMG showed a fourfold increase in amplitude compared to maximal voluntary contractions. --- Explanation: Objective EMG amplitude amplification supports abnormal neuromuscular circuit excitability as a proximal event.

[PMID:28215594] [INDIRECT EVIDENCE] [SUPPORT] Electroneuromyography showed abnormal spontaneous activity. --- Explanation: Additional electrophysiologic evidence supports neuromuscular hyperexcitability as a proximal mechanism.


MONDO:0010922

[PMID:32429959] [INDIRECT EVIDENCE] [SUPPORT] Histological data revealed predominantly lymphoplasmacytic inflammatory infiltrate that can affect any section of the digestive tract. --- Explanation: Histological evidence confirms inflammatory infiltration of the GI tract consistent with autoimmune-mediated enteropathy.

[PMID:17405137] [INDIRECT EVIDENCE] [SUPPORT] We present a patient with this syndrome having a unique "mesh-like" mucosal change radiographically and white granules endoscopically in the gastrointestinal tract. --- Explanation: Independent endoscopic/radiographic mucosal abnormalities further support GI tissue pathology in Satoyoshi syndrome.


MONDO:0010922

[PMID:32429959] [INDIRECT EVIDENCE] [SUPPORT] Chronic diarrhea was the main digestive symptom (92.3%). Other symptoms such as abdominal pain (15.4%), nausea (7.7%) and vomiting (7.7%), were less frequent. The D-xylose test was positive in 10 out of 12 patients, and 9 out of 13 cases showed a flattened oral glucose tolerance test suggesting carbohydrate malabsorption. --- Explanation: Clinical testing demonstrates carbohydrate malabsorption and its close association with chronic diarrhea.

[PMID:32429959] [INDIRECT EVIDENCE] [SUPPORT] Chronic diarrhea may be severe and result in malnutrition, anemia, growth retardation, cachexia, disability and even death. --- Explanation: This links prolonged gastrointestinal dysfunction to downstream growth consequences.

[PMID:32429959] [INDIRECT EVIDENCE] [SUPPORT] Chronic diarrhea with malabsorption is one of the most disabling symptoms in SS. --- Explanation: This conclusion-level statement directly supports clinically significant absorptive dysfunction.


MONDO:0010922

[PMID:31217029] [INDIRECT EVIDENCE] [SUPPORT] Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. --- Explanation: Systematic review confirms alopecia as one of the main symptoms present in 100% of reported cases.

[PMID:36749015] [INDIRECT EVIDENCE] [SUPPORT] All cases had painful muscular spasms and alopecia. --- Explanation: The larger 77-case review confirms alopecia as a universal feature, supporting an upstream follicular injury mechanism.


MAXO:0000640

[PMID:31217029] [SUPPORT] 28 out of 30 cases responded to a regimen that included costicosteroids. --- Explanation: Systematic review demonstrates that corticosteroid-containing regimens produced favorable responses in the large majority of treated cases.

[PMID:32429959] [SUPPORT] In 6 out of 10 patients, diarrhea improved with a treatment regimen that included corticosteroids. --- Explanation: Corticosteroid-containing regimens specifically improved gastrointestinal symptoms, supporting the inflammatory/autoimmune basis of the enteropathy.

[PMID:32429959] [SUPPORT] None of the three patients who died had received corticosteroids or immunosuppressants. --- Explanation: The observation that all fatal cases lacked immunosuppressive treatment suggests corticosteroids may reduce mortality, though publication bias must be considered.


MAXO:0000324

[PMID:31217029] [SUPPORT] Dantrolene improved muscle symptoms in 13 out of 15 cases, but not any other symptoms of the disease. --- Explanation: Dantrolene is effective for muscle spasm control but does not address the underlying autoimmune process or other systemic manifestations.


MAXO:0000058

[PMID:31217029] [SUPPORT] Other immunosuppressive drugs including cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus and cyclophosphamide were used to decrease corticosteroid dose or improve efficacy. --- Explanation: Multiple immunosuppressive agents have been employed as steroid-sparing therapy in Satoyoshi syndrome.


MAXO:0000058

[PMID:31217029] [PARTIAL] Immunoglobulin therapy was used in nine patients and four of them obtained a favorable response. --- Explanation: IVIG produced favorable responses in less than half of treated patients, indicating variable efficacy.


HGNC.SYMBOL:No established monogenic etiology

[PMID:31217029] [SUPPORT] Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. --- Explanation: This review explicitly states that disease etiology remains unknown.

[PMID:16972238] [SUPPORT] Although an autoimmune origin of Satoyoshi syndrome seems likely, its exact etiology remains as yet unknown, as is the origin of the involuntary contractions. --- Explanation: Electrophysiology-focused case study confirms unresolved etiology despite autoimmune evidence.


MONDO:0004525

[PMID:30755943] [PARTIAL] The authors describe a clinical case of crusted scabies with pruritus and exuberant cutaneous lesions. --- Explanation: The abstract reports pruritus in scabies.


MONDO:0004525

[PMID:30755943] [PARTIAL] The authors describe a clinical case of crusted scabies with pruritus and exuberant cutaneous lesions. --- Explanation: The abstract reports cutaneous lesions consistent with rash.


MAXO:0000058

[PMID:35298417] [SUPPORT] Mass treatment with permethrin cream or ivermectin can be given directly to patients. --- Explanation: The abstract notes permethrin cream or ivermectin for treatment.


CHEBI:34911

[PMID:35298417] [INDIRECT EVIDENCE] [SUPPORT] Mass treatment with permethrin cream or ivermectin can be given directly to patients. --- Explanation: The abstract notes permethrin cream or ivermectin for treatment.


CHEBI:6078


NCBITaxon:52283

[PMID:35298417] [SUPPORT] Scabies is a contagious parasitic skin disease caused by Sarcoptes scabiei infestation which can be transmitted through direct or indirect contact. --- Explanation: The abstract identifies S. scabiei infestation as the cause of scabies.


MONDO:0015254

[PMID:24698483] [SUPPORT] anaemia, growth stunting, impaired cognition, and decreased physical fitness --- Explanation: Schistosomiasis is associated with anaemia in the listed systemic effects.


MONDO:0015254

[PMID:24698483] [SUPPORT] severe hepatosplenism --- Explanation: Hepatosplenism reflects hepatosplenic involvement consistent with hepatosplenomegaly.


MONDO:0015254

[PMID:30093684] [INDIRECT EVIDENCE] [SUPPORT] Eggs trapped in the surrounding tissues and organs, such as the liver and bladder, cause inflammatory immune responses (including granulomas) --- Explanation: Trapped eggs drive inflammatory granulomas in liver and bladder tissue.


MONDO:0015254


MONDO:0015254

[PMID:24698483] [INDIRECT EVIDENCE] [SUPPORT] periportal fibrosis with portal hypertension --- Explanation: The review links egg-induced pathology to periportal fibrosis and portal hypertension.


MAXO:0000058

[PMID:24698483] [SUPPORT] treatment once every 1 or 2 years with the isoquinolinone drug, praziquantel, to suppress morbidity --- Explanation: The review describes periodic praziquantel treatment as standard preventive therapy.


NCBITaxon:6181

[PMID:30093684] [SUPPORT] caused by parasitic flatworms (blood flukes) of the genus Schistosoma --- Explanation: The review identifies Schistosoma blood flukes as the causative agents.


MONDO:0005090

[PMID:28437056] [SUPPORT] Schizophrenia symptoms fall into six common symptom clusters: delusions and hallucinations, disorganization of speech, cognitive dysfunction, negative symptoms, affective symptoms, and motor system abnormalities. --- Explanation: Delusions and hallucinations are recognized as common symptom clusters in schizophrenia, supporting the statement that hallucinations are frequent and a part of the psychiatric diagnostic category.

[PMID:25773224] [PARTIAL] Schizophrenia is a complex mental disorder associated with not only cognitive dysfunctions, such as memory and attention deficits, but also changes in basic sensory processing. --- Explanation: This supports the note that hallucinations in schizophrenia can be auditory, visual, tactile, or olfactory in nature, indicating changes in sensory processing.

[PMID:21545448] [SUPPORT] Prevalence of OHs and hallucinations in other modalities differed according to the WHO-10 international centre. Across centres, OHs were present in 13% of the WHO-10 dataset, similar to the 17% prevalence rate in the SAPS/SANS dataset. --- Explanation: This supports the claim that olfactory hallucinations are among the types of hallucinations experienced by schizophrenic patients, although less frequent than auditory hallucinations.

[PMID:35383683] [PARTIAL] We found that a substantial proportion of patients could not clearly distinguish between thinking and hallucinating. The emotional tone of the voices increased in negativity. --- Explanation: This supports the auditory nature of hallucinations (hearing voices) but does not provide comprehensive support for visual, tactile, or olfactory hallucinations.


MONDO:0005090

[PMID:33485408] [PARTIAL] Delusions are commonly conceived as false beliefs that are held with certainty and which cannot be corrected. This conception of delusion has been influential throughout the history of psychiatry and continues to inform how delusions are approached in clinical practice and in contemporary schizophrenia research. --- Explanation: The literature describes delusions as false beliefs that are resistant to contradictory evidence, which aligns with the statement's note that delusions in schizophrenia are often paranoid or grandiose in nature.

[PMID:949230] [PARTIAL] The underlying diagnosis of Capgras delusion is not found to be exclusively paranoid schizophrenia, nor is the sex exclusively female, as once was believed. --- Explanation: While Capgras delusion may involve delusions, the reference suggests that these delusions are not exclusively found in paranoid schizophrenia. This partially supports the statement but adds another layer of complexity.

[PMID:29151090] [NO_EVIDENCE] Non-bizarre delusion, defined as a false belief possible although highly unlikely, is the main manifestation of delusional disorders, previously known as paranoia. --- Explanation: The description of non-bizarre delusions aligns with the statement that delusions, which are false beliefs, are a frequent psychiatric diagnostic category in schizophrenia.

[PMID:24677735] [PARTIAL] Persecutory and/or grandiose delusions were more strongly associated with each offender group compared with non-offenders, most so with late first offenders. --- Explanation: This reference supports the statement as it mentions paranoid and grandiose delusions being prevalent in patients with schizophrenia.


MONDO:0005090

[PMID:27206569] [INDIRECT EVIDENCE] [PARTIAL] Findings have converged to suggest early dysregulation in the striatum, especially in the rostral caudate, manifesting as excess synthesis and release. Recent data showed deficit extending to most cortical regions and even to other extrastriatal subcortical regions not previously considered to be 'hypodopaminergic' in schizophrenia. --- Explanation: While the literature supports dopamine dysregulation in various brain regions, it does not specifically emphasize the mesolimbic and mesocortical pathways alone.

[PMID:24986384] [INDIRECT EVIDENCE] [NO_EVIDENCE] A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic). --- Explanation: The abstract does not provide specific information supporting the imbalance of dopamine transmission specifically in the mesolimbic and mesocortical pathways as described in the statement.

[PMID:1981107] [INDIRECT EVIDENCE] [NO_EVIDENCE] This article discusses the possibility that a deficient activity within the cortico-striatal glutamatergic pathway is an important pathophysiological component in some cases of schizophrenia and that glutamatergic agonists may prove beneficial in this disorder. --- Explanation: The study focuses on glutamate dysregulation rather than dopamine transmission dysregulation in mesolimbic and mesocortical pathways.

[PMID:24128684] [INDIRECT EVIDENCE] [PARTIAL] This clinical picture is generally associated with supersensitivity to dopamine, and activates dopamine neurotransmission that is usually alleviated or blocked by drugs that block dopamine D2 receptors. --- Explanation: There is an implication of dopamine dysregulation, but the specifics of mesolimbic and mesocortical pathways are not confirmed.


MONDO:0005090

[PMID:11532718] [INDIRECT EVIDENCE] [SUPPORT] Research has implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of schizophrenia. --- Explanation: The literature specifically states that glutamatergic neurotransmission dysfunction is associated with the pathophysiology of schizophrenia, supporting the provided statement.

[PMID:28754595] [INDIRECT EVIDENCE] [SUPPORT] Accumulating evidence suggests that synaptic plasticity is impaired in schizophrenia. Given the role of synaptic plasticity in learning, memory, and neural circuit maturation, impaired plasticity may underlie many features of the schizophrenia syndrome. --- Explanation: The literature discusses the impairment of synaptic plasticity in schizophrenia and its interaction with brain maturation, aligning with the statement.

[PMID:29954475] [INDIRECT EVIDENCE] [SUPPORT] Psychosis is now widely hypothesized to involve neural networks beyond the classical dopaminergic mesolimbic pathway, including serotonin and glutamate systems as well. --- Explanation: This reference supports the involvement of glutamatergic systems in schizophrenia, reinforcing the statement.

[PMID:22351070] [INDIRECT EVIDENCE] [SUPPORT] Schizophrenia is believed to result from problems during neural development that lead to improper function of synaptic transmission and plasticity, and in agreement, many of the susceptibility genes encode proteins critical for neural development. --- Explanation: The literature supports the idea that schizophrenia impacts synaptic transmission and plasticity, specifically implicating glutamatergic, GABAergic, dopaminergic, and cholinergic synapses.


MONDO:0005090


MONDO:0005090

[PMID:10372507] [INDIRECT EVIDENCE] [SUPPORT] At the cellular level, gamma-aminobutyric acid (GABA)-ergic interneurons are a common feature in psychotic states... and are themselves synchronised by the ascending dopamine and serotonin innervations. --- Explanation: The literature highlights that GABAergic interneurons play a significant role in the cellular characteristics found in psychotic states, including schizophrenia.

[PMID:22308256] [INDIRECT EVIDENCE] [SUPPORT] Disturbances in glutamate and GABAergic neurotransmission may underlie the pathophysiology of schizophrenia. --- Explanation: This reference directly states that disturbances in GABAergic neurotransmission may underlie the pathophysiology of schizophrenia.

[PMID:34584230] [INDIRECT EVIDENCE] [SUPPORT] Reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders. --- Explanation: This meta-analysis supports the idea that reduced GABA levels and thus GABAergic dysfunction are related to the pathophysiology of schizophrenia.

[PMID:25432637] [INDIRECT EVIDENCE] [SUPPORT] Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia. --- Explanation: The abnormalities in GABAergic receptors in schizophrenia support the idea of GABAergic signaling abnormalities being part of the disorder’s pathophysiology.

[PMID:22351070] [INDIRECT EVIDENCE] [SUPPORT] Here, we will review evidence for altered neurotransmission at ... GABAergic ... synapses in schizophrenia... --- Explanation: This article reviews evidence for altered GABAergic neurotransmission in schizophrenia, supporting the stated claim.


MAXO:0000058

[PMID:12769630] [PARTIAL] With the use of chlorpromazine and other traditional antipsychotics for psychosis, it was soon discovered that the antipsychotic efficacy of this class of medications was closely associated with their ability to block dopamine D(2) receptors in the brain. --- Explanation: This reference supports the statement that antipsychotic medications act through dopamine D2 receptor antagonism. It also mentions medications like clozapine, risperidone, and others, but does not specifically mention olanzapine in this context.

[PMID:8626371] [PARTIAL] The introduction of novel antipsychotic agents, such as clozapine and risperidone, has enhanced the clinicians' ability to manage schizophrenic patients. --- Explanation: This supports the usage of clozapine and risperidone but does not detail the mechanism focused on dopamine D2 receptor antagonism.

[PMID:8823348] [PARTIAL] Clozapine has shown to be effective in some poor or partially responsive patients in three prospective, random assignment, double-blind trials. --- Explanation: Supports effectiveness of clozapine in treatment-resistant patients but does not address dopamine D2 receptor antagonism directly.

[PMID:32464195] [PARTIAL] To improve treatment efficacy during the critical early stages of schizophrenia, we aimed to identify molecular signatures at baseline (T0) for prediction of a positive response to the atypical antipsychotics olanzapine and risperidone after 6 weeks (T6) treatment. --- Explanation: This supports the use of olanzapine and risperidone but does not detail the mechanism involving dopamine D2 receptor antagonism.

[PMID:17845145] [PARTIAL] The drug discovery process has focused mostly on targeting D2 dopamine receptors. --- Explanation: This reference supports the focus on D2 dopamine receptors in drug discovery, which aligns with the mechanism described.


MAXO:0000077

[PMID:20880828] [SUPPORT] There is good evidence from a considerable number of clinical trials that CBTp has a consistent clinical benefit when used in addition to standard care. --- Explanation: This indicates that Cognitive Behavioral Therapy (CBT) is a recognized treatment for schizophrenia that aims at changing maladaptive thought patterns and behaviors.

[PMID:27335156] [SUPPORT] Cognitive behavioural therapy for psychosis and cognitive remediation are 2 psychosocial interventions that have demonstrated positive outcomes for violence in SCZ. --- Explanation: This highlights that CBT, which focuses on changing maladaptive thought patterns and behaviors, is effective in treating certain symptoms of schizophrenia.

[PMID:17716100] [PARTIAL] A theoretical analysis of schizophrenia based on a cognitive model integrates the complex interaction of predisposing neurobiological, environmental, cognitive, and behavioral factors with the diverse symptomatology. --- Explanation: The statement aligns with the cognitive approach to schizophrenia, which underpins CBT.

[PMID:31699627] [NO_EVIDENCE] Cognitive remediation is now widely recognized as an effective treatment for cognitive deficits in schizophrenia. --- Explanation: Although this reference focuses on cognitive remediation, it aligns with the efficacy of cognitive therapies like CBT.


MAXO:0000077

[PMID:16885207] [SUPPORT] Social skills training consists of learning activities utilizing behavioral techniques that enable persons with schizophrenia and other disabling mental disorders to acquire interpersonal disease management and independent living skills for improved functioning in their communities. --- Explanation: The study states that social skills training helps individuals with schizophrenia to improve functioning in their communities by acquiring interpersonal and independent living skills.

[PMID:31708048] [SUPPORT] Common elements to these interventions include building a therapeutic alliance, recovery orientation, education, and skills training, which can be directed to a range of targets, including problem-solving, communication, social skills, and social cognition. --- Explanation: Clinical therapies for first-episode psychosis as part of coordinated specialty care (CSC) include skills training directed at social skills.

[PMID:23773889] [PARTIAL] METHODOLOGY: Social skills training, cognitive behavioral therapy, cognitive remediation, and social cognitive training therapy paradigms were searched and the extant literature is summarized for each, with particular focus on: 1) the rationale for treatment methodology; 2) particular methods of treatment; and, 3) meta-analytic data regarding their efficacy and/or effectiveness. --- Explanation: This reference indicates that social skills training is a recognized psychosocial method used to treat schizophrenia and discusses its efficacy.

[PMID:36050663] [SUPPORT] Although pharmacological treatments can often lessen the psychotic symptoms that are a hallmark of schizophrenia, they do not lessen the social and cognitive deficits that create the greatest impediments to community engagement and functional recovery. --- Explanation: The study compares Cognitive Enhancement Therapy and Social Skills Training (HOPES/SST), highlighting their role in improving social and community functioning.

[PMID:32614046] [PARTIAL] To address this need, we have developed SocialVille-an online, plasticity-based training program that targets SC deficits in schizophrenia...These results provide support for the efficacy of a remote, plasticity-based social cognitive training program in improving SC and social functioning in schizophrenia. --- Explanation: The study shows that social cognitive training programs, which could include elements similar to Social Skills Training, improve social functioning in schizophrenia patients.

[PMID:21860049] [PARTIAL] Intention-to-treat analyses found significantly larger pre-post improvements with TAR than with CRT in prosodic affect recognition, ToM, and social competence and a trend effect in global social functioning. --- Explanation: The study indicates that training aimed at social cognition, such as TAR, may improve social skills and functions, relevant to social skills training programs.


MAXO:0000950

[PMID:15176765] [SUPPORT] This article posits that the positive findings for supportive therapy (ST) in recent trials may indicate an important but undervalued aspect of psychosocial interventions for schizophrenia. --- Explanation: The article discusses the benefits of supportive therapy in schizophrenia treatment and emphasizes mechanisms such as the therapeutic alliance and social support, indicating that ongoing support helps manage daily life and stress.

[PMID:23244011] [SUPPORT] The intervention group improved significantly on measures of both PANSS and GAF scores, with large effect sizes at two years follow-up after inclusion. Further, improvement on GAF(function) (p = 0.000) and GAF(symptom) (p = 0.010) significantly favored SPP in combination with TaU over TaU alone. --- Explanation: Supportive psychodynamic psychotherapy, a variant of supportive therapy, was found to significantly improve symptoms and functional outcomes, underscoring its role in ongoing support for managing stress and daily life in schizophrenia.

[PMID:31708048] [SUPPORT] Group, individual, and family therapies in CSC aim to help the client and family understand and cope with the experience of psychosis, promote symptomatic and functional recovery and improve quality of life, and support the pursuit of personally meaningful goals of the client. --- Explanation: Coordinated specialty care, including supportive interventions, focuses on coping, recovery, and quality of life, indicating the importance of ongoing support.


MAXO:0001351

[PMID:8749891] [PARTIAL] Most vocational rehabilitation programs have a positive influence on work-related activities, but most have failed to show substantial and enduring impacts on independent, competitive employment. --- Explanation: While vocational rehabilitation programs have positive influences on work-related activities, they have not generally shown substantial and enduring impacts on competitive employment.

[PMID:31327504] [PARTIAL] At the end of two years in the service, 829 (70.4%) patients were meaningfully employed and 348 (29.6%) patients were unemployed. --- Explanation: Vocational programs have shown promise with a significant portion of patients being gainfully employed, but it does not necessarily indicate maintaining stable employment over long periods.

[PMID:18715755] [SUPPORT] NET training improved vocational outcomes, suggesting the value of combining cognitive remediation with other rehabilitation methods to enhance functional outcomes. --- Explanation: Neurocognitive enhancement therapy combined with vocational services showed improved employment outcomes, supporting the positive impact on gaining and maintaining employment.

[PMID:32393158] [SUPPORT] Veterans in the hybrid condition, compared with the AFVP alone, were more likely to find employment, had higher rates of full-time employment, and earned significantly more money over the course of the study. --- Explanation: Blended vocational services significantly improved employment outcomes, supporting the effectiveness of vocational rehabilitation in gaining and maintaining employment.

[PMID:29135426] [SUPPORT] Significantly higher employment rate and longer job tenure were found in the ISE group (63.0%, 29.56 wk) compared with the IPS group (50.0%, 25.47 wk) and TVR group (33.3%, 9.91 wk). --- Explanation: Integrated supported employment led to higher employment rates and longer job tenure, indicating that such vocational rehabilitation can help with gaining and maintaining employment.


HGNC.SYMBOL:DRD2


HGNC.SYMBOL:GRIN1


HGNC.SYMBOL:GRIN2A


HGNC.SYMBOL:GAD1


HGNC.SYMBOL:RELN


HGNC.SYMBOL:C4A


HGNC.SYMBOL:C3


HGNC.SYMBOL:DISC1

[PMID:30286368] [PARTIAL] DISC1 gene has been shown as a risk factor for schizophrenia in some reports. --- Explanation: The meta-analysis confirms associations between specific SNPs in the DISC1 gene and schizophrenia risk.

[PMID:24056909] [NO_EVIDENCE] Questions about DISC1 as a genetic risk factor for schizophrenia. --- Explanation: This reference raises questions about the role of DISC1 as a risk factor, implying a lack of consensus.

[PMID:30285728] [PARTIAL] The human DISC1 gene is located on chromosome 1 and is highly associated with schizophrenia and other mental disorders. --- Explanation: This study associates the DISC1 gene with schizophrenia among other mental disorders, supporting its role as a risk factor.

[PMID:20302823] [NO_EVIDENCE] Modeling the disease in genetically tractable animals is thus a challenging but increasingly important task. In this review, I discuss the potential problems and perspectives associated with modeling schizophrenia in fruit flies, and briefly review the recent studies analyzing the molecular and cellular functions of Disrupted-In-Schizophrenia-1 (DISC1) in transgenic flies. --- Explanation: This review highlights the relevance of studying DISC1 functions in the context of schizophrenia.


HGNC.SYMBOL:COMT

[PMID:23573605] [SUPPORT] COMT is an enzyme that is distributed widely throughout the brain, but seems to be uniquely relevant to how dopamine affects information-processing in the prefrontal cortex. There is a common variation in the genetic sequence of the COMT gene, which causes a dramatic change in its enzyme activity. In people with schizophrenia, in their healthy siblings, and also in normal controls, the COMT genotype predicts 4% of the variation in human executive cognition and working memory. We have thus identified a genetic mechanism in the human species that affects the efficiency and efficacy of information-processing in the prefrontal cortex. It is, also, a weak genetic risk factor for schizophrenia: in family studies, it increases the risk of schizophrenia by 50-80%. --- Explanation: The COMT gene is identified as a weak genetic risk factor for schizophrenia, increasing the risk by 50-80% in family studies.


HGNC.SYMBOL:NRG1

[PMID:16520822] [PARTIAL] Our meta-analysis provides support for the association of NRG1 with schizophrenia, but indicates that firmly establishing the role of NRG1 gene in schizophrenia by genetic association requires much larger sample sizes than have hitherto been reported. --- Explanation: The meta-analysis found some evidence supporting the association of NRG1 with schizophrenia, but also highlighted the need for larger sample sizes to firmly establish this role.

[PMID:15162166] [SUPPORT] Recently, the gene that encodes neuregulin-1 (NRG1) has been identified as a potential susceptibility gene for schizophrenia, and defects in the expression of erbB3, one of the NRG1 receptors, have been shown to occur in the prefrontal cortex of schizophrenic patients... --- Explanation: This reference identifies NRG1 as a potential susceptibility gene for schizophrenia, indicating a genetic association.

[PMID:20600464] [SUPPORT] We mainly focus on genes including:...NRG1 (Neuregulin 1)... Taken together there is converging evidence for the contribution of genes potentially related to alterations in intracellular Ca-homeostasis to the risk of schizophrenia. --- Explanation: This review points to NRG1 as a gene potentially related to the risk of schizophrenia.

[PMID:24968777] [SUPPORT] ...It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1... --- Explanation: This paper focuses on NRG1 as one of the risk genes associated with schizophrenia.


HGNC.SYMBOL:DTNBP1

[PMID:19862852] [SUPPORT] This study shows that DTNBP1 is a risk gene for schizophrenia in EAs. Variation at DTNBP1 may modify risk for schizophrenia in this population. --- Explanation: This reference provides evidence that DTNBP1 is associated with an increased risk of schizophrenia, particularly in European-Americans.

[PMID:18474210] [SUPPORT] To date, DTNBP1 has provided the greatest evidence of illness modification, as associations with negative and cognitive symptoms and worse outcome have been published in independent samples. --- Explanation: This reference elaborates on the association of DTNBP1 with specific clinical features of schizophrenia, further supporting its role as a risk factor.

[PMID:24968777] [SUPPORT] It considers models for understanding the role(s) of risk genes, with a particular focus on DTNBP1 and NRG1, their interactions with environmental factors, and with each other (epistasis). --- Explanation: This reference discusses the role of DTNBP1 as a risk gene for schizophrenia within the context of genetic and environmental interactions.


ECTO:0100005

[PMID:24957864] [PARTIAL] Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use. --- Explanation: The study suggests that there is an association between cannabis use and schizophrenia, but it indicates that the genetic components might play a significant role, making it partially supportive.

[PMID:26232243] [SUPPORT] Individuals with a history of cannabis abuse had an earlier age at onset by nearly six years. --- Explanation: The study provides direct evidence that cannabis use is associated with an earlier age at onset of psychosis.

[PMID:21068828] [SUPPORT] onset is associated with environmental factors such as early life adversity, growing up in an urban environment, minority group position and cannabis use. --- Explanation: The association of environmental factors, including cannabis use, supports the idea of increased risk of schizophrenia.

[PMID:28142064] [PARTIAL] The relationship between age at psychosis onset and COMT Val158Met and BDNF Val66Met polymorphisms with early cannabis use as well as those factors associated with early cannabis use were investigated. --- Explanation: The study highlights the important role of early cannabis use and genetic polymorphisms in influencing the age at psychosis onset, thereby supporting the statement.

[PMID:37185055] [PARTIAL] Tobacco use was associated with an earlier age at psychosis onset...; however, these results were no longer significant after controlling for cannabis use. --- Explanation: The study indicates that cannabis use correlates with an earlier age at onset of psychosis, supporting the statement.


MONDO:0010013

[PMID:3799723] [SUPPORT] flattened, hypoplastic vertebral bodies --- Explanation: Original description documents severely flattened vertebral bodies as a characteristic radiographic feature.

[PMID:19508970] [SUPPORT] severe flattening of the vertebral bodies with absent ossification of the posterior parts of the vertebral bodies --- Explanation: Multi-family study confirms severe platyspondyly with deficient posterior ossification as a hallmark feature.


MONDO:0010013

[PMID:3799723] [SUPPORT] hypoplastic iliac bones with "a snail-like" configuration --- Explanation: Original description identifies the snail-like iliac configuration as pathognomonic.

[PMID:19508970] [SUPPORT] The radiological hallmark of SBD is the snail-like configuration of the hypoplastic iliac bone --- Explanation: Confirms that the snail-like iliac configuration is the radiological hallmark.


MONDO:0010013

[PMID:3799723] [SUPPORT] short, broad long-bones with dumbbell-like appearance; short and wide fibula --- Explanation: Original description documents severe limb shortening with characteristic dumbbell-shaped long bones.

[PMID:19508970] [SUPPORT] short thick long bones --- Explanation: Multi-family study confirms characteristic short thick long bones.


MONDO:0010013

[PMID:3799723] [SUPPORT] short, broad long-bones with dumbbell-like appearance --- Explanation: Original description identifies the dumbbell-like long bone morphology.

[PMID:35934917] [SUPPORT] short and broad long bones with a dumbbell-like appearance, thoracic hypoplasia --- Explanation: Later report confirms dumbbell-shaped long bones as characteristic even in milder cases.


MONDO:0010013

[PMID:3799723] [SUPPORT] short ribs --- Explanation: Original description identifies short ribs as a cardinal feature.

[PMID:19508970] [SUPPORT] The chest was narrow and bell shaped. --- Explanation: Multi-family study describes the narrow bell-shaped thorax caused by short ribs.


MONDO:0010013

[PMID:3799723] [SUPPORT] precocious ossification of the tarsus --- Explanation: Original description identifies precocious tarsal ossification as a distinguishing feature.

[PMID:19508970] [SUPPORT] Tarsal ossification was advanced --- Explanation: Confirmed in subsequent multi-family study.


MONDO:0010013

[PMID:11200994] [SUPPORT] this is the first report of Schneckenbecken dysplasia with the development of hydrops early in the second trimester --- Explanation: Documents hydrops fetalis developing in the second trimester in a confirmed case.

[PMID:19508970] [SUPPORT] This fetus was identified on 18 weeks ultrasound as having hydrops and short limbs --- Explanation: Additional case with hydrops detected on prenatal ultrasound.


MONDO:0010013

[PMID:19508970] [SUPPORT] The autopsy revealed placental hydropic changes, pulmonary hypoplasia and accessory spleen --- Explanation: Autopsy confirmation of pulmonary hypoplasia in a classic case.


MONDO:0010013

[PMID:17952091] [INDIRECT EVIDENCE] [SUPPORT] Here we created Slc35d1-deficient mice that develop a lethal form of skeletal dysplasia with severe shortening of limbs and facial structures --- Explanation: Slc35d1 knockout mice recapitulate the lethal skeletal dysplasia phenotype, confirming the gene's role in skeletal development.

[PMID:17952091] [INDIRECT EVIDENCE] [SUPPORT] These mice had short, sparse chondroitin sulfate chains caused by a defect in chondroitin sulfate biosynthesis --- Explanation: Demonstrates that SLC35D1 deficiency directly impairs chondroitin sulfate chain formation.

[PMID:19508970] [INDIRECT EVIDENCE] [SUPPORT] Yeast complementation assay showed the T65P mutant protein lost the transporter activity of nucleotide sugars --- Explanation: Functional assay demonstrates that the disease-causing missense mutation abolishes nucleotide-sugar transport activity.


MONDO:0010013


MONDO:0010013

[PMID:17952091] [INDIRECT EVIDENCE] [SUPPORT] Epiphyseal cartilage in homozygous mutant mice showed a decreased proliferating zone with round chondrocytes, scarce matrices and reduced proteoglycan aggregates --- Explanation: Mouse model demonstrates growth plate disorganization with decreased proliferation, round chondrocytes, and depleted matrix.

[PMID:3799723] [INDIRECT EVIDENCE] [SUPPORT] Chondro-osseous histology is characteristic with hypervascularity, increased cellular density, and normal size chondrocytes with a centrally located round nucleus and absence of lacunar space --- Explanation: Original human histopathology description confirms characteristic growth plate findings.

[PMID:11200994] [INDIRECT EVIDENCE] [SUPPORT] The histology showed hypercellular and hypervascular cartilage with chondrocytes with centrally located nucleus --- Explanation: Additional human case confirms the characteristic cartilage histology with hypercellularity and hypervascularization.


MAXO:0000079


hgnc:20800

[PMID:17952091] [SUPPORT] We also identified that loss-of-function mutations in human SLC35D1 cause Schneckenbecken dysplasia, a severe skeletal dysplasia --- Explanation: Initial identification of SLC35D1 as the causative gene through combined human and mouse genetic studies.

[PMID:19508970] [SUPPORT] We identified four novel mutations, c.319C>T (p.R107X), IVS4+3A>G, a 4959-bp deletion causing the removal of exon 7 (p.R178fsX15), and c.193A>C (p. T65P), in three SBD families --- Explanation: Documents the spectrum of SLC35D1 loss-of-function mutations in multiple families from different ethnic backgrounds.

[PMID:19508970] [SUPPORT] Our findings suggest that SLC35D1 loss-of-function mutations result consistently in SBD and are exclusive to SBD --- Explanation: Demonstrates that SLC35D1 mutations are specific to Schneckenbecken dysplasia within the severe spondylodysplastic dysplasias group.

[PMID:31423530] [SUPPORT] SLC35D1 acts as a general UDP-sugar transporter and that the p.(Pro133Leu) mutation resulted in a significant decrease in transport activity --- Explanation: Biochemical characterization shows that hypomorphic mutations reduce but do not abolish transport activity, correlating with milder phenotype.

[PMID:35934917] [SUPPORT] This is the first case report of a family with a novel likely pathogenic variant (p. Met134Thr) and mild phenotypic features --- Explanation: Demonstrates the milder end of the SLC35D1 phenotypic spectrum with surviving patients showing short stature and mild skeletal anomalies.


hgnc:6080

[PMID:25997753] [SUPPORT] apparent loss of INPPL1 function can produce either the perinatal lethal Schneckenbecken dysplasia phenotype or non-lethal opsismodysplasia --- Explanation: Identifies INPPL1 as a second locus for Schneckenbecken dysplasia with an allelic spectrum including opsismodysplasia.


MONDO:0010013

[PMID:3799723] [SUPPORT] a distinct neonatal lethal chondrodysplasia inherited as an autosomal recessive trait --- Explanation: Original description establishes autosomal recessive inheritance pattern.

[PMID:19508970] [SUPPORT] Schneckenbecken dysplasia (SBD) is an autosomal recessive lethal skeletal dysplasia that is classified into the severe spondylodysplastic dysplasias (SSDD) group in the international nosology for skeletal dysplasias --- Explanation: Confirms autosomal recessive inheritance and nosology classification.


MONDO:0015987

[PMID:16638549] [SUPPORT] Scimitar syndrome is a rare congenital anomaly consisting in part of right pulmonary venous return to the inferior vena cava. --- Explanation: Review confirming anomalous pulmonary venous return to the IVC as the defining feature.


MONDO:0015987

[PMID:34396590] [SUPPORT] Associated cardiac and extracardiac defects, particularly hypoplasia of the right lung, are present in up to three-quarters of cases. --- Explanation: Review of 92 published investigations confirming right lung hypoplasia in up to 75% of cases.


MONDO:0015987

[PMID:35804238] [PARTIAL] Patients diagnosed with SS under the age of one year had a significantly greater incidence of congenital heart defects (CHD) (p < 0.001), non-cardiac anomalies (p = 0.02), pulmonary hypertension (p = 0.02), and mortality (p = 0.04) compared to those diagnosed over the age of 1 year. --- Explanation: Three-decade study of 84 patients showing pulmonary hypertension is significantly more common in infantile-onset cases.


MONDO:0015987

[PMID:34396590] [PARTIAL] On long term follow-up, one sixth of patients reported persistent dyspnoea and recurrent respiratory infections. --- Explanation: Review reporting persistent recurrent respiratory infections in one-sixth of patients on long-term follow-up, even after surgical management.


MONDO:0015987

[PMID:38634941] [SUPPORT] six (54.55%) cardiac dextroposition --- Explanation: Tertiary center series documenting cardiac dextroposition in 55% of scimitar syndrome patients.


MONDO:0015987

[PMID:34396590] [SUPPORT] up to four-fifths presented during infancy, with cardiac failure, increased pulmonary flow, and pulmonary hypertension. --- Explanation: Review noting that up to 80% of infant presentations include cardiac failure.


MONDO:0015987

[PMID:16638549] [INDIRECT EVIDENCE] [PARTIAL] In this article, we review the historical aspects, presentation, and pathophysiology of Scimitar syndrome and discuss available treatment strategies. --- Explanation: Review covering the developmental pathophysiology underlying scimitar syndrome.


MONDO:0015987


MONDO:0015987

[PMID:16638549] [INDIRECT EVIDENCE] [SUPPORT] Scimitar syndrome is a rare congenital anomaly consisting in part of right pulmonary venous return to the inferior vena cava. --- Explanation: Review establishing the core anatomic defect of anomalous right pulmonary venous drainage to the IVC.

[PMID:38634941] [INDIRECT EVIDENCE] [SUPPORT] Scimitar Syndrome is part of a complex spectrum of congenital cardiovascular anomalies related to anomalous pulmonary venous return. --- Explanation: Colombian tertiary-center series confirming scimitar syndrome as a complex spectrum of anomalous pulmonary venous return anomalies.

[PMID:40110298] [INDIRECT EVIDENCE] [PARTIAL] a unique vessel, identified as the Scimitar vein, was found draining into the left portal vein. --- Explanation: Rare variant with scimitar vein draining into the portal vein rather than the IVC, causing portal hypertension and esophageal varices in a child.


MONDO:0015987

[PMID:34396590] [INDIRECT EVIDENCE] [SUPPORT] Associated cardiac and extracardiac defects, particularly hypoplasia of the right lung, are present in up to three-quarters of cases. --- Explanation: Review of 92 published investigations confirming right lung hypoplasia is present in up to 75% of scimitar syndrome cases.

[PMID:38634941] [INDIRECT EVIDENCE] [SUPPORT] six (54.55%) cardiac dextroposition, six (54.55%) pulmonary hypoplasia, five (45.45%) right pulmonary artery hypoplasia --- Explanation: Tertiary center series quantifying the frequency of pulmonary hypoplasia (55%), dextroposition (55%), and right pulmonary artery hypoplasia (45%) in scimitar syndrome.


MONDO:0015987

[PMID:38634941] [INDIRECT EVIDENCE] [PARTIAL] three (27.27%) had aortopulmonary collaterals. Four (36.36%) patients had horseshoe lungs, and four (36.36%) had bronchopulmonary sequestration. --- Explanation: Tertiary center series documenting the frequency of aortopulmonary collaterals (27%) and bronchopulmonary sequestration (36%) as associated anomalies.

[PMID:29054305] [INDIRECT EVIDENCE] [PARTIAL] Noninfants exhibited lower incidences of right pulmonary artery hypoplasia (p < 0.001), aortopulmonary collaterals (p = 0.004) --- Explanation: Large cohort showing aortopulmonary collaterals are significantly more common in infantile than non-infantile forms.


MONDO:0015987

[PMID:35804238] [INDIRECT EVIDENCE] [PARTIAL] PH, CHD, neonatal SS diagnosis, ECMO support, and markedly elevated scimitar vein pressure are associated with mortality. --- Explanation: Three-decade single-center study of 84 patients identifying pulmonary hypertension as a major mortality risk factor.

[PMID:36093138] [INDIRECT EVIDENCE] [PARTIAL] High-risk factors of death included age at diagnosis (p = 0.000), PH (p = 0.007) and PVS (p = 0.014). --- Explanation: Retrospective analysis of 34 patients confirming pulmonary hypertension and pulmonary vein stenosis as independent risk factors for mortality.


MONDO:0015987

[PMID:38634941] [INDIRECT EVIDENCE] [SUPPORT] two (18.18%) patients were found to have an atrial septal defect, three (27.27%) ventricular septal defect, and one (9%) had Tetralogy of Fallot. --- Explanation: Tertiary center series documenting ASD in 18% of scimitar syndrome patients.

[PMID:29054305] [INDIRECT EVIDENCE] [NO_EVIDENCE] Forty-seven patients were identified, including 20 infants with significant associated congenital heart defects (42.6%, including 7 with single ventricle physiology) --- Explanation: Columbia cohort showing 43% of patients had significant associated cardiac defects, with ASD being among the most common.


MONDO:0015987

[PMID:38634941] [INDIRECT EVIDENCE] [SUPPORT] two (18.18%) patients were found to have an atrial septal defect, three (27.27%) ventricular septal defect, and one (9%) had Tetralogy of Fallot. --- Explanation: Tertiary center series documenting VSD in 27% of scimitar syndrome patients.


MONDO:0015987

[PMID:29054305] [INDIRECT EVIDENCE] [NO_EVIDENCE] Forty-seven patients were identified, including 20 infants with significant associated congenital heart defects (42.6%, including 7 with single ventricle physiology) --- Explanation: Columbia cohort documenting the spectrum of associated cardiac defects including great vessel anomalies.


MONDO:0015987

[PMID:29054305] [INDIRECT EVIDENCE] [SUPPORT] Forty-seven patients were identified, including 20 infants with significant associated congenital heart defects (42.6%, including 7 with single ventricle physiology) --- Explanation: Cohort showing 15% of scimitar syndrome patients had single ventricle physiology, the most severe end of associated cardiac anomalies.

[PMID:38634941] [INDIRECT EVIDENCE] [SUPPORT] two (18.18%) patients were found to have an atrial septal defect, three (27.27%) ventricular septal defect, and one (9%) had Tetralogy of Fallot. --- Explanation: Tertiary center series documenting Tetralogy of Fallot in 9% of scimitar syndrome patients.

[PMID:41625720] [INDIRECT EVIDENCE] [SUPPORT] The cardiac anomalies included right atrial isomerism, persistent left superior vena cava, unbalanced complete atrioventricular (AV) atrial septal defect with atresia of the left component of the AV valve and a hypoplastic left ventricle, double outlet right ventricle, malposition of the great arteries, and anomalous origin of left pulmonary artery (AOLPA) from the perihilar portion of the right pulmonary artery. --- Explanation: First reported case of left-sided scimitar with horseshoe lung and complex CHD including heterotaxy, single ventricle, and DORV, demonstrating the extreme end of the spectrum.


MAXO:0000004

[PMID:34396590] [SUPPORT] Overall operative mortality has been cited between 4.8% and 5.9%. Mortality was highest in patients with preoperative pulmonary hypertension, and those undergoing surgery in infancy. Despite timely surgical intervention, post-repair obstruction of the scimitar vein, intra-atrial baffle obstruction, or stenosis of the inferior caval vein were reported in up to two-thirds of cases. --- Explanation: Comprehensive review of surgical outcomes noting 5-6% operative mortality but significant postoperative vein obstruction rates.

[PMID:34318016] [SUPPORT] None of the 11 patients who only had the new procedure developed pulmonary vein obstruction during postoperative monitoring up to 3.6 years. --- Explanation: Boston Children's Hospital series showing a new multipatch technique eliminated postoperative pulmonary vein obstruction in 11 patients, compared to 45% obstruction rate with traditional techniques.

[PMID:29054305] [SUPPORT] Multivariable analyses identified infantile onset as an independent risk factor for stenosis or obstruction after repair (hazard ratio 9.34, p = 0.048) --- Explanation: Columbia cohort identifying infantile onset as a 9-fold independent risk factor for postoperative stenosis.


MAXO:0000004

[PMID:34396590] [INDIRECT EVIDENCE] [SUPPORT] Overall operative mortality has been cited between 4.8% and 5.9%. Mortality was highest in patients with preoperative pulmonary hypertension, and those undergoing surgery in infancy. Despite timely surgical intervention, post-repair obstruction of the scimitar vein, intra-atrial baffle obstruction, or stenosis of the inferior caval vein were reported in up to two-thirds of cases. --- Explanation: Comprehensive review of surgical outcomes noting 5-6% operative mortality but significant postoperative vein obstruction rates.

[PMID:34318016] [INDIRECT EVIDENCE] [SUPPORT] None of the 11 patients who only had the new procedure developed pulmonary vein obstruction during postoperative monitoring up to 3.6 years. --- Explanation: Boston Children's Hospital series showing a new multipatch technique eliminated postoperative pulmonary vein obstruction in 11 patients, compared to 45% obstruction rate with traditional techniques.

[PMID:29054305] [INDIRECT EVIDENCE] [SUPPORT] Multivariable analyses identified infantile onset as an independent risk factor for stenosis or obstruction after repair (hazard ratio 9.34, p = 0.048) --- Explanation: Columbia cohort identifying infantile onset as a 9-fold independent risk factor for postoperative stenosis.


MAXO:0000004


MAXO:0001389

[PMID:36093138] [SUPPORT] Eight patients received interventional catheter therapy, including occlusion of aortopulmonary collateral arteries (APCs) and other intracardiac malformations, without the following surgery. --- Explanation: East China center series showing catheter-based therapy is effective as a standalone intervention in selected patients.

[PMID:41556875] [PARTIAL] All the patients underwent successfully a transcatheter occlusion of SV at the IVC junction using occlusion devices allowing proximal re-rerouting to the left atrium through the fistula. Aberrant systemic artery arising from the abdominal aorta was embolized in 2 cases during the same intervention. --- Explanation: French series of 3 patients with dual-drainage scimitar variant successfully treated by transcatheter occlusion of the IVC connection, redirecting flow to the left atrium.

[PMID:41070433] [PARTIAL] All four patients (three children, one adult) had dual drainage of right pulmonary veins into the inferior caval vein and to the left atrium via a connecting vein. All patients underwent a successful catheter occlusion of the anomalous connection to the systemic vein without complication. --- Explanation: International multicentre series of 4 patients confirming transcatheter correction of the dual-drainage scimitar variant as a safe and effective alternative to surgery.


MAXO:0001389

[PMID:36093138] [INDIRECT EVIDENCE] [SUPPORT] Eight patients received interventional catheter therapy, including occlusion of aortopulmonary collateral arteries (APCs) and other intracardiac malformations, without the following surgery. --- Explanation: East China center series showing catheter-based therapy is effective as a standalone intervention in selected patients.

[PMID:41556875] [INDIRECT EVIDENCE] [PARTIAL] All the patients underwent successfully a transcatheter occlusion of SV at the IVC junction using occlusion devices allowing proximal re-rerouting to the left atrium through the fistula. Aberrant systemic artery arising from the abdominal aorta was embolized in 2 cases during the same intervention. --- Explanation: French series of 3 patients with dual-drainage scimitar variant successfully treated by transcatheter occlusion of the IVC connection, redirecting flow to the left atrium.

[PMID:41070433] [INDIRECT EVIDENCE] [PARTIAL] All four patients (three children, one adult) had dual drainage of right pulmonary veins into the inferior caval vein and to the left atrium via a connecting vein. All patients underwent a successful catheter occlusion of the anomalous connection to the systemic vein without complication. --- Explanation: International multicentre series of 4 patients confirming transcatheter correction of the dual-drainage scimitar variant as a safe and effective alternative to surgery.


MAXO:0000950

[PMID:38634941] [SUPPORT] Medical management is effective for mild to moderate cases. --- Explanation: Clinical series confirming conservative management is appropriate for mild to moderate scimitar syndrome.


MAXO:0000950

[PMID:38634941] [INDIRECT EVIDENCE] [SUPPORT] Medical management is effective for mild to moderate cases. --- Explanation: Clinical series confirming conservative management is appropriate for mild to moderate scimitar syndrome.


HGNC.SYMBOL:Genetic underpinnings

[PMID:34210367] [PARTIAL] A molecular genetic diagnosis was made in 7 of 18 cases (39% of those tested). Ninety-six per cent of the cohort had some type of extracardiac finding, with 43% having asthma and 20% having a gastrointestinal pathology. --- Explanation: Texas Children's Hospital cohort of 89 patients showing 39% diagnostic yield from genetic testing and high prevalence of extracardiac findings.


MONDO:0017838

[PMID:11181578] [SUPPORT] characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected --- Explanation: Describes the generalized skeletal involvement with prominent cranial hyperostosis.


MONDO:0017838

[PMID:11181578] [PARTIAL] Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur --- Explanation: Hearing loss results from cranial nerve foramen narrowing.


MONDO:0017838

[PMID:11181578] [SUPPORT] facial nerve palsy, hearing loss and atrophy of the optic nerves can occur --- Explanation: Facial nerve palsy is a recognized complication of cranial foramen narrowing.


MONDO:0017838

[PMID:11179006] [INDIRECT EVIDENCE] [PARTIAL] the SOST gene encodes an important new regulator of bone homeostasis --- Explanation: Confirms SOST as a key regulator of bone metabolism.


MONDO:0017838


MONDO:0017838

[PMID:11181578] [INDIRECT EVIDENCE] [SUPPORT] Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur --- Explanation: Cranial nerve foramen narrowing from progressive bone overgrowth causes neurological complications.


MAXO:0000079


HGNC.SYMBOL:SOST Mutations

[PMID:11181578] [SUPPORT] Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients --- Explanation: Identifies the three types of SOST mutations in sclerosteosis.

[PMID:11179006] [SUPPORT] Affected Afrikaners carry a nonsense mutation near the amino terminus of the encoded protein, whereas an unrelated affected person of Senegalese origin carries a splicing mutation within the single intron of the gene --- Explanation: Details the specific mutations in Afrikaner and Senegalese patients.


MONDO:0009412

[PMID:37366866] [SUPPORT] Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. --- Explanation: Perifollicular hemorrhage is explicitly listed as a common manifestation of scurvy.


MONDO:0009412

[PMID:37366866] [SUPPORT] Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. --- Explanation: Ecchymoses are explicitly listed as a common manifestation of scurvy.

[PMID:37915623] [SUPPORT] He was diagnosed with scurvy due to a long history of staying indoors and inadequate intake of fruits or vegetables. --- Explanation: The case report describes a patient presenting with ecchymoses of both lower extremities, demonstrating this as a key clinical feature.


MONDO:0009412

[PMID:37366866] [SUPPORT] Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. --- Explanation: Gingival bleeding is explicitly listed as a common manifestation.


MONDO:0009412

[PMID:37366866] [SUPPORT] Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. --- Explanation: Arthralgias are explicitly listed as a common manifestation.

[PMID:37915623] [SUPPORT] Here, we report on a 25-year-old male patient without any underlying conditions who presented with severe pain and ecchymoses of both lower extremities. --- Explanation: The case demonstrates severe pain in the lower extremities as a presenting feature of scurvy.


MONDO:0009412

[PMID:37915623] [SUPPORT] Scurvy, resulting from vitamin C deficiency, has nonspecific constitutional symptoms, including weakness, malaise, and fatigue. --- Explanation: Weakness, malaise, and fatigue are described as nonspecific constitutional symptoms of scurvy.


MONDO:0009412

[PMID:37366866] [SUPPORT] Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. --- Explanation: Impaired wound healing is explicitly listed as a common manifestation.


MAXO:0000109

[PMID:37366866] [SUPPORT] It can be adequately treated and prevented via vitamin C supplementation. --- Explanation: This confirms that vitamin C supplementation is the adequate treatment and prevention for scurvy.


MONDO:0006608

[PMID:40965095] [SUPPORT] Seborrheic dermatitis is a chronic inflammatory skin condition characterized by erythematous patches and plaques with white-to-yellow greasy scale often localized to the scalp and face. --- Explanation: This abstract directly supports greasy scaling as a defining phenotype of seborrheic dermatitis.


MONDO:0006608

[PMID:40965095] [SUPPORT] Seborrheic dermatitis is a chronic inflammatory skin condition characterized by erythematous patches and plaques with white-to-yellow greasy scale often localized to the scalp and face. --- Explanation: This supports erythematous lesions as a core clinical manifestation of seborrheic dermatitis.


MONDO:0006608

[PMID:20592880] [SUPPORT] It may be associated with pruritus, and it primarily affects sebum-rich areas, such as the scalp, face, upper chest, and back. --- Explanation: This overview explicitly identifies pruritus as a common symptom of seborrheic dermatitis.


MONDO:0006608

[PMID:40965095] [SUPPORT] Notably, in patients with more richly pigmented skin, postinflammatory pigment alteration can also be a feature of seborrheic dermatitis, highlighting the importance of considering skin colour differences in the diagnosis. --- Explanation: This review supports pigment alteration as an additional phenotype in seborrheic dermatitis, especially in richly pigmented skin.


MONDO:0006608

[PMID:35967915] [INDIRECT EVIDENCE] [SUPPORT] Seborrheic dermatitis (SD) is a common chronic inflammatory skin disorder that mostly affects young adults in areas rich in sebaceous glands (scalp, face, and trunk). --- Explanation: This supports sebaceous-rich localization as a core organizing feature of seborrheic dermatitis biology.


MONDO:0006608

[PMID:27072777] [INDIRECT EVIDENCE] [SUPPORT] Conclusion: The effect of lithium succinate on growth of M. yeasts and presumably in SD can be explained by a precipitation of free fatty acids as alkali soaps limiting their availability for the growth of these lipid-dependent yeasts. --- Explanation: This abstract supports free fatty acids as a mechanistically relevant Malassezia-associated intermediate in seborrheic dermatitis.


MONDO:0006608

[PMID:16283346] [INDIRECT EVIDENCE] [SUPPORT] When keratinocytes were infected with M. furfur, an up-regulation for TLR2, MyD88, HBD-2, HBD-3 and IL-8 mRNA was demonstrated, compared to the untreated cells. --- Explanation: This supports a distinct keratinocyte innate-sensing step in response to Malassezia.


MONDO:0006608


MONDO:0006608

[PMID:16283346] [INDIRECT EVIDENCE] [SUPPORT] The M. furfur-induced increase in HBD-2 and IL-8 gene expression is inhibited by anti-TLR2 neutralising antibodies, suggesting that TLR2 is involved in the M. furfur-induced expression of these molecules. --- Explanation: This supports a distinct mediator-induction step downstream of keratinocyte TLR2 sensing.


MONDO:0006608

[PMID:25267545] [INDIRECT EVIDENCE] [SUPPORT] Our results identify Malassezia spp. as potential strong inducers of pro-inflammatory responses when taken up by antigen-presenting cells and identify C-type lectin receptors and the NLRP3 inflammasome as crucial actors in this process. --- Explanation: This supports NLRP3 inflammasome activation as a separate mechanistic node rather than a bundled catch-all process.


MONDO:0006608

[PMID:22670617] [INDIRECT EVIDENCE] [SUPPORT] The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. --- Explanation: This transcriptomic study identifies lipid-metabolic repression as a distinct lesional abnormality in dandruff/seborrheic dermatitis.


MONDO:0006608

[PMID:40965103] [INDIRECT EVIDENCE] [SUPPORT] current evidence points to a complex interplay between 3 key factors: skin microbiome dysbiosis involving Malassezia spp. overgrowth and alterations in bacterial composition, dysregulated inflammatory responses in the skin, and skin barrier dysfunction. --- Explanation: This supports skin barrier dysfunction as one of the principal mechanistic axes in seborrheic dermatitis.


MONDO:0006608

[PMID:22670617] [INDIRECT EVIDENCE] [SUPPORT] The most striking feature of lesional skin relative to normal was the reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. --- Explanation: This study supports an active inflammatory lesional state as a distinct mechanistic feature.


MONDO:0006608

[PMID:41089687] [INDIRECT EVIDENCE] [SUPPORT] SSD lesional scalps demonstrated significantly greater expressions of proteins related to T-cell/lymphocyte activation, the cytokine storm signaling pathway and the CGAS-STING signaling pathway. Ingenuity pathway analysis (IPA) highlighted Th1 skewing. --- Explanation: This provides direct human lesional evidence for a Th1-biased immune node in seborrheic dermatitis.


MONDO:0006608

[PMID:41153741] [INDIRECT EVIDENCE] [SUPPORT] Advances in transcriptomic and microbiome profiling have revealed a complex immunoinflammatory environment in SD, involving predominantly Th1, Th17, and Th22 axes. --- Explanation: This identifies Th17 and Th22 pathways as additional inflammatory axes in seborrheic dermatitis.


MAXO:0000058

[PMID:35967915] [SUPPORT] In adults, mild-to-moderate scalp SD forms can be managed with topical antifungals (ketoconazole, ciclopirox, miconazole) or antiinflammatory (mild-to-moderate potency corticosteroids) or keratolytic/humectant (propylene glycol) agents. --- Explanation: This supports topical antifungals as standard therapy for mild-to-moderate scalp seborrheic dermatitis.


MAXO:0000058

[PMID:40965088] [SUPPORT] Topical therapies, including antifungals and anti-inflammatory agents such as corticosteroids and calcineurin inhibitors, are the mainstay of treatment of mild-to-moderate seborrheic dermatitis. --- Explanation: This supports topical anti-inflammatory therapy as a mainstay of seborrheic dermatitis management.


MAXO:0000058

[PMID:40965088] [SUPPORT] The recent development of new treatments, such as the topical phosphodiesterase-4 inhibitor (roflumilast 0.3% foam), shows promise in providing effective, noncorticosteroid options for seborrheic dermatitis management. --- Explanation: This supports roflumilast foam as an emerging nonsteroidal treatment for seborrheic dermatitis.


NCBITaxon:55193

[PMID:40965103] [SUPPORT] current evidence points to a complex interplay between 3 key factors: skin microbiome dysbiosis involving Malassezia spp. overgrowth and alterations in bacterial composition, dysregulated inflammatory responses in the skin, and skin barrier dysfunction. --- Explanation: This review supports Malassezia overgrowth as part of the dysbiotic microbial component of seborrheic dermatitis rather than as a stand-alone infectious mechanism.

[PMID:35967915] [SUPPORT] In adults, several environmental triggers are likely to promote SD development, along with fungal colonization by Malassezia spp., sebaceous gland activity, as well as immunosuppression, endocrine, neurogenic and iatrogenic factors. --- Explanation: This review places Malassezia colonization among multiple interacting contributors to adult seborrheic dermatitis.


MONDO:0001200

[PMID:37115960] [SUPPORT] Hypertension (HTN) that can be attributed to a particular source is known as secondary HTN (SH). --- Explanation: The abstract defines secondary hypertension as hypertension attributable to a specific cause.


MONDO:0010857

[PMID:41089414] [SUPPORT] Semantic dementia (SD) is a progressive neurodegenerative disorder primarily characterized by core linguistic deficits, notably impaired confrontation naming and single-word comprehension. --- Explanation: Impaired confrontation naming corresponds to anomic aphasia.


MONDO:0010857

[PMID:41089414] [PARTIAL] Associated features include surface dyslexia, prosopagnosia, relatively preserved speech production, and emotional or behavioral abnormalities. --- Explanation: The abstract lists surface dyslexia as an associated feature of semantic dementia.


MONDO:0010857

[PMID:41089414] [SUPPORT] Associated features include surface dyslexia, prosopagnosia, relatively preserved speech production, and emotional or behavioral abnormalities. --- Explanation: The abstract lists prosopagnosia as an associated feature of semantic dementia.