Expanding the Genotype-Phenotype Correlation of Marden-Walker Syndrome due to PIEZO2 Gene Variants: A Case Report...

Marden-Walker syndrome (MWS; OMIM 248700) is an extremely rare congenital disorder characterized by multiple joint contractures, craniofacial dysmorphism, neurological abnormalities, and multisystem involvement. Although historically diagnosed on clinical grounds, only a few cases have been molecularly confirmed. Here, we describe a Brazilian female infant with classic manifestations of MWS, carrying a heterozygous pathogenic variant in the PIEZO2 gene not previously reported in MWS. To our knowledge, this is the first molecularly confirmed MWS case from Brazil, thus expanding both the genotype-phenotype spectrum and geographic distribution of PIEZO2-related disorders. Comparative analysis of previously reported molecularly confirmed cases reveals shared core features and highlights the prominent neurological involvement observed in our patient. A review of individuals with the same PIEZO2 variant demonstrates marked phenotypic variability-from Gordon syndrome to distal arthrogryposis type 5-underscoring allelic heterogeneity and variable expressivity. This case refines the phenotypic spectrum of PIEZO2-related disorders and illustrates how allelic heterogeneity contributes to wide clinical variability, while also underscoring the importance of including underrepresented populations in variant interpretation.