Autosomal recessive MALTA syndrome with compound heterozygous MYH9 variants

Distinguishing microcystic adnexal carcinoma from MALTA (MYH9-associated elastin aggregation) syndrome is critical to prevent unnecessary aggressive surgery. We define a variant of MALTA histologically characterized by benign deep syringoid ductal proliferation with elastic fiber aggregation (denoted as MALTA-BDSDP). A male in his early twenties presented with bilateral facial lesions. Germline sequencing identified 3 heterozygous MYH9 variants: c.1363G>A (p.Gly455Ser) in the motor domain and c.4490G>A (p.Arg1497Gln) and c.4876A>G (p.Ile1626Val) in the tail domain. To our knowledge, Gly455Ser and Arg1497Gln represent previously unreported variants that show Mendelian segregation in this family. The proband inherited Gly455Ser and Ile1626Val in cis from one parent and Arg1497Gln from the other, resulting in compound heterozygosity. His sibling carried identical variants but remained asymptomatic, demonstrating incomplete penetrance. Molecular modeling predicted that these sequence variants destabilize Myosin-9 through disrupted coiled-coil interactions and altered local packing. Uniquely, compound heterozygosity in the affected sibling suggests an autosomal recessive inheritance pattern, contrasting with previously reported dominant MALTA cases and expanding the known genetic spectrum. Histopathology revealed preserved myoepithelial architecture, an absence of perineural invasion, and pathognomonic elastic fiber aggregates, features distinguishing MALTA-BDSDP from microcystic adnexal carcinoma. These findings prevent misdiagnosis and enable appropriate genetic counseling.

Abstract from PubMed