Myhre syndrome

Myhre syndrome (also known as LAPS syndrome — Laryngotracheal stenosis, Arthropathy, Prognathism, and Short stature syndrome) is a rare connective tissue disorder caused by pathogenic variants in the SMAD4 gene, which plays a critical role in the TGF-beta signaling pathway. The condition affects multiple body systems and is characterized by short stature, skeletal anomalies (including thickened calvaria, brachydactyly, broad ribs, and limited joint mobility), distinctive facial features (midface hypoplasia, short palpebral fissures, prognathism, and a short philtrum), muscular build, and intellectual disability of variable severity. Hearing loss, both conductive and sensorineural, is frequently observed. Additional features include restrictive and obstructive lung disease, laryngotracheal stenosis, pericardial and pleural fibrosis, and cardiovascular abnormalities such as congenital heart defects and progressive fibrotic complications. Skin may appear thickened, and affected individuals often have a distinctive stiff or firm consistency to subcutaneous tissues. Behavioral features, including autism spectrum traits, have been reported in some patients. There is currently no cure for Myhre syndrome, and management is supportive and multidisciplinary. Treatment focuses on addressing specific symptoms, including surgical intervention for airway stenosis, hearing aids or cochlear implants for hearing loss, cardiac monitoring, speech and occupational therapy, and educational support. Close surveillance for progressive fibrotic complications, particularly involving the airways and cardiovascular system, is essential. Given the role of dysregulated TGF-beta signaling, research into targeted therapies is ongoing but no specific pharmacological treatment has been established.

Common questions about Myhre syndrome