Biallelic MYH3 Variants Cause Distal Arthrogryposis in Compound Heterozygosity and a Subclinical Phenotype in Simple...

Distal arthrogryposis constitutes a highly heterogeneous group of disorders with a critical need for clear classification. Phenotypes have traditionally been characterized using the classification system proposed by Bamshad or Hall for distal arthrogryposis. Recessive MYH3 inheritance has been described in contractures, pterygia and spondylocarpotarsal fusion syndrome, and, more recently, in distal arthrogryposis without skeletal fusion. We hereby report a nuclear family affected by distal arthrogryposis with biallelic MYH3-related disorder, identifying two novel variants, which in the heterozygous state yield a subclinical phenotype. Beyond refining the molecular diagnosis and guiding genetic counseling, our study emphasizes that the classification of MYH3-related disorders and their inheritance modes is still evolving, underscoring the need to integrate knowledge gained from careful analyses.