Expanding the Genetic and Phenotypic Spectrum of Mowat‐Wilson Syndrome: A Study of 10 Turkish Patients With an Intrafamilial Recurrence Caused by First Intragenic Large Deletion

Mowat-Wilson syndrome (MWS) is a complex disorder caused by heterozygous ZEB2 gene variations creating haploinsufficiency. The main clinical features are evolving facial dysmorphism, intellectual disability, eye and brain malformations, and various organ anomalies. Our study examines 10 Turkish patients, who had clinical diagnosis, underwent evaluation, clinical investigations, and genetic tests in multiple tertiary centers across Türkiye, and were molecularly diagnosed with MWS. Molecular analysis with sequencing techniques alongside array testing unveiled disease-causing variations in addition to novel variants, including two siblings with recurrent multiexon deletion. Clinical presentations varied, featuring neurodevelopmental delay and characteristic facial traits and organ malformations across all cases, alongside less frequently reported manifestations such as laryngomalacia or rocker bottom feet in addition to new features such as macroorchidism and osteoporosis. Our findings expand the genetic and phenotypical spectrum of MWS, and hint at potential implications of gonadal mosaicism. While establishing clear genotype-phenotype correlations poses challenges, comprehensive genetic testing remains pivotal for precise diagnosis and management. The study highlights the complexity of MWS genetics, with potential implications of gonadal mosaicism on recurrence. Further research is needed to elucidate mechanisms driving phenotypic variability, potential hotspots, and mechanisms for recurrent variations. We report on the largest cohort with MWS from Türkiye.