Expanding the Genotype–Phenotype Correlation of Marden–Walker Syndrome due to PIEZO2 Gene Variants: A Case Report From Brazil

ABSTRACT 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.