Weill-Marchesani syndrome: a comprehensive review of pathogenesis, clinical features, and management

Weill-Marchesani syndrome is a rare genetic connective tissue disorder, with an estimated prevalence of approximately 1 in 100,000 individuals. It is characterized by a pleiotropic set of manifestations, including short stature, brachydactyly, joint stiffness, ocular abnormalities, and cardiovascular complications. The syndrome follows either an autosomal recessive or autosomal dominant inheritance pattern, with pathogenic variants identified in the FBN1, ADAMTS10, ADAMTS17, and LTBP2 genes. This review examines the current understanding of Weill-Marchesani syndrome pathogenesis, clinical presentation, diagnostic approaches, and treatment strategies. Diagnosis relies on a combination of genetic testing and clinical evaluation. The autosomal dominant form, primarily associated with FBN1 mutations, is typically characterized by lens ectopia and joint stiffness. In contrast, the autosomal recessive form, resulting from mutations in ADAMTS10, ADAMTS17, or LTBP2, is predominantly linked to microspherophakia and cardiovascular abnormalities. Ophthalmological manifestations, including severe myopia and an increased risk of angle-closure glaucoma, are crucial for diagnosis. Management requires a multidisciplinary approach, incorporating ophthalmological interventions such as iridotomy or lensectomy, cardiological monitoring, and orthopedic care. This review synthesizes findings from literature published between 2015 and early 2025, highlighting the ongoing challenges in establishing definitive diagnostic criteria. The analysis underscores the need for further research into the molecular mechanisms underlying Weill-Marchesani syndrome and the development of targeted therapeutic strategies.