Weiss-Kruszka syndrome (WSKA; OMIM #618619), also termed ZNF462-related disorder, is a rare autosomal dominant multiple congenital anomaly syndrome caused by haploinsufficiency of ZNF462(zinc finger protein 462; OMIM 617371) at chromosome 9q31.2. The condition was first delineated by Weiss et al. and further characterised by Kruszka et al. It is defined by a recognisable pattern of craniofacial features (most consistently ptosis, together with metopic ridging or craniosynostosis), variable and usually mild global developmental delay, and a high frequency of autistic features.
Fewer than 50 affected individuals have been reported to date (approximately 48 in the published literature by early 2026); the true prevalence is unknown, and the disorder is very likely under-recognised, particularly in adults who have not undergone contemporary genomic testing. One reported individual was alive at 67 years, and lifespan is not known to be reduced.
Inheritance is autosomal dominant, with complete penetrance but marked variable expressivity, including within families (the intrafamilial phenotype can range from isolated ptosis to corpus callosum agenesis with metopic craniosynostosis). Approximately 95% of cases arise from a de novo variant; about 5% are inherited from an affected, and sometimes only mildly affected, parent. Parental germline mosaicism has been reported.
ZNF462