FLNA Variants Related to Melnick-Needles Syndrome: Two Mexican Case Reports and a Comprehensive Variant Review.

Melnick-Needles Syndrome (MNS; OMIM #309350) is a rare X-linked dominant osteochondrodysplasia caused by FLNA gain-of-function variants. It is characterized by short stature, facial dysmorphism, skeletal anomalies, and systemic complications. FLNA encodes Filamin A, a cytoskeletal protein with over 90 binding partners. Variants in FLNA cause a broad spectrum of disorders, among which MNS represents one of the most severe phenotypes. Despite increasing research on MNS, many aspects of its genetic and phenotypic spectrum remain unknown. In this work, we presented two Mexican cases with a diagnosis of MNS with different FLNA missense variants p.(Leu1193Pro) and p.(Ser1199Leu). In addition, we performed a comprehensive review of the literature about FLNA variants related to MNS. This study reinforced the genetic and phenotypic complexity of MNS, emphasizing the critical role of exon 22 variants in the pathogenesis of the disease.