A major phenotypic hallmark of individuals with PSMC3 variants is the predominance of neurodevelopmental or neuropsychiatric symptoms. All the affected individuals identified so far have developmental delay, characterized by speech delay, intellectual disability, and motor delay. Brain magnetic resonance imaging highlighted frequent anomalies, whereas abnormal behavior and seizures are more inconstant. Most individuals display dysmorphic facial features, including notably tall or broad forehead, thin upper lip with down-turned corners of mouth, abnormal palate, epicanthal folds, and orofacial clefts. Malformations are commonly observed, notably in skeleton (scoliosis, acetabular dysplasia, brachymetatarsy), heart (ventricular or septal defects, patent ductus arteriosus, pulmonary hypertension and atresia), kidney (horseshoe shape, pelvicalyceal dilatation, nephrocalcinosis, and multi-cystic dysplastic kidney), and head (microcephaly; relative to severe macrocephaly. About half of the individuals experienced growth failure, with feeding difficulties, whereas slightly less individuals have a hearing loss (sensorineural or conductive ). Tumors have been noted in two individuals (craniopharyngioma and neuroblastoma).
PSMC3