Mandibuloacral dysplasia

Mandibuloacral dysplasia (MAD) is a rare genetic disorder belonging to the group of laminopathies and progeroid syndromes. It is characterized by skeletal abnormalities including underdevelopment of the mandible (lower jaw) and clavicles (collarbones), along with delayed closure of cranial sutures, acro-osteolysis (resorption of the terminal finger and toe bones), joint contractures, and short stature. The condition also affects the skin and subcutaneous tissue, causing lipodystrophy (abnormal distribution of body fat), skin atrophy, mottled hyperpigmentation, and features of premature aging (progeria) such as alopecia and dental crowding. Two main subtypes are recognized based on the pattern of lipodystrophy and underlying genetic cause. Type A (MADA), caused by mutations in the LMNA gene encoding lamin A/C, is associated with partial lipodystrophy predominantly affecting the extremities. Type B (MADB), caused by mutations in the ZMPSTE24 gene (also known as FACE1), tends to present with more generalized lipodystrophy and a more severe phenotype. Metabolic complications including insulin resistance, glucose intolerance, and dyslipidemia are common in both subtypes and may lead to diabetes mellitus and cardiovascular complications. There is currently no cure for mandibuloacral dysplasia. Treatment is supportive and multidisciplinary, focusing on management of metabolic abnormalities (such as diabetes and hyperlipidemia), orthopedic complications, dental issues, and dermatological manifestations. Regular monitoring of metabolic parameters and cardiac function is recommended. Genetic counseling is important for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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