Lipodystrophies

In the last two decades, great progress has been made in refining the classification and elucidating the molecular basis of genetic lipodystrophies, rare disorders characterized by selective loss of body fat and predisposition to insulin resistance and its metabolic complications such as diabetes mellitus, hypertriglyceridemia, and hepatic steatosis. The autosomal recessive, congenital generalized lipodystrophy is due to mutations in AGPAT2, BSCL2, CAV1, and PTRF; and autosomal dominant familial partial lipodystrophy (FPLD) is due to mutations in LMNA, PPARG, AKT2, and PLIN1. Among extremely rare syndromes, autosomal recessive, mandibuloacral dysplasia is due to LMNA and ZMPSTE24 mutations and an autoinflammatory lipodystrophy syndrome due to PSMB8 mutations. SHORT syndrome is due to mutations in PIK3R1 and mandibular hypoplasia, deafness, progeroid features syndrome due to POLD1 mutation. The precise mode of inheritance and molecular genetic bases of many extremely rare forms of genetic lipodystrophies remain to be elucidated.