NORD gratefully acknowledges Guiseppe Novelli, MD, Department of Biopathology and Diagnostic Imaging, University of Rome, Italy and Maria Rosaria D'Apice, MD, Laboratory of Medical Genetics, University of Rome, Italy, for assistance in the preparation of this report.
Mandibuloacral dysplasia (MAD) is an extremely rare genetic disorder characterized by underdevelopment (hypoplasia) of the lower jaw (mandible) and the collarbone (clavicle), bone loss at the ends of the fingers and toes (acro-osteolysis), skin degeneration (cutaneous atrophy), and partial lipodystrophy, a condition marked by selective loss of body fat (adipose tissue) from various areas of the body. Cutaneous atrophy and lipodystrophy may contribute to affected children having a prematurely-aged appearance (progeroid features). Lipodystrophy may be associated with clinical features of metabolic syndrome including insulin resistance, impaired glucose tolerance, and diabetes mellitus. Additional symptoms can occur as well. Two types of mandibuloacral dysplasia have been identified, type A and type B. Both types are inherited as autosomal recessive conditions. Mandibuloacral dysplasia type A (MADA) is caused by mutations of the lamin A/C (LMNA) gene; mandibuloacral dysplasia type B (MADB) is caused by mutations of the zinc metalloproteinase (ZMPSTE24) gene.
Mandibuloacral dysplasia may be classified as a form of lipodystrophy or progeria because of its overlapping symptoms. Mandibuloacral dysplasia type A may also be classified as a laminopathy, a general term for the group of disorders associated with a mutation of the LMNA gene. The ZMPSTE24 mutation that causes mandibuloacral dysplasia type B can also cause restrictive dermopathy syndrome.
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