Research Information System
Molecular Syndromology, vol.17, no.1, pp.90-95, 2026 (SCI-Expanded, Scopus)
Introduction: Weiss-Kruszka syndrome is a rare, autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the ZNF462, located at chromosome 9p31.2. Clinically, it is characterized by craniofacial dysmorphism, global developmental delay, intellectual disability, short stature, congenital anomalies of the heart and brain, and feeding difficulties. The phenotypic spectrum is notably heterogeneous, with variable expressivity and occasional incomplete penetrance. Case Presentation: Herein, we report a novel de novo heterozygous frameshift variant in ZNF462, designated c.2924del; p.(Gln975ArgfsTer3) (NM_021224.6), identified in a pediatric patient. Conclusion: Importantly, our patient presented with a congenital diaphragmatic hernia – an anomaly not previously described in association with Weiss-Kruszka syndrome. To date, 48 cases have been reported in the literature. Our findings further broaden the phenotypic spectrum linked to ZNF462 variants and emphasize the need for continued clinical and molecular characterization. Through the detailed documentation of this unique case, we aimed to enhance the understanding of the clinical variability and potential comorbidities associated with this emerging syndrome.