Familial partial lipodystrophy type 1 (FPLD1), or Kobberling-type lipodystrophy, is characterized by loss of adipose tissue confined to the extremities, with normal or increased distribution of fat on the face, neck, and trunk (Kobberling and Dunnigan, 1986). For a general description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.

Familial partial lipodystrophy (FPLD) is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution beginning in late childhood or early adult life. Affected individuals gradually lose fat from the upper and lower extremities and the gluteal and truncal regions, resulting in a muscular appearance with prominent superficial veins. In some patients, adipose tissue accumulates on the face and neck, causing a double chin, fat neck, or cushingoid appearance. Metabolic abnormalities include insulin-resistant diabetes mellitus with acanthosis nigricans and hypertriglyceridemia; hirsutism and menstrual abnormalities occur infrequently. Familial partial lipodystrophy may also be referred to as lipoatrophic diabetes mellitus, but the essential feature is loss of subcutaneous fat (review by Garg, 2004). The disorder may be misdiagnosed as Cushing disease (see 219080) (Kobberling and Dunnigan, 1986; Garg, 2004). Genetic Heterogeneity of Familial Partial Lipodystrophy Familial partial lipodystrophy is a clinically and genetically heterogeneous disorder. Types 1 and 2 were originally described as clinical subtypes: type 1 (FPLD1; 608600), characterized by loss of subcutaneous fat confined to the limbs (Kobberling et al., 1975), and FPLD2, characterized by loss of subcutaneous fat from the limbs and trunk (Dunnigan et al., 1974; Kobberling and Dunnigan, 1986). No genetic basis for FPLD1 has yet been delineated. FPLD3 (604367) is caused by mutation in the PPARG gene (601487) on chromosome 3p25; FPLD4 (613877) is caused by mutation in the PLIN1 gene (170290) on chromosome 15q26; FPLD5 (615238) is caused by mutation in the CIDEC gene (612120) on chromosome 3p25; FPLD6 (615980) is caused by mutation in the LIPE gene (151750) on chromosome 19q13; FPLD7 (606721) is caused by mutation in the CAV1 gene (601047) on chromosome 7q31; FPLD8 (620679), caused by mutation in the ADRA2A gene (104210) on chromosome 10q25; and FPLD9 (620683), caused by mutation in the PLAAT3 gene (613867) on chromosome 11q12.

Familial partial lipodystrophy type 3 (FPLD3) is an autosomal dominant disorder characterized by marked loss of subcutaneous fat from the extremities. Calves and lower arms appear prominently muscular. Excess subcutaneous facial, neck, suprascapular, and abdominal fat may be present. Patients have insulin resistance, dyslipidemia, and hypertension, and develop type 2 diabetes (summary by Hegele et al., 2002, Agarwal and Garg, 2002). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.

Mandibuloacral dysplasia with type B lipodystrophy (MADB) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies such as mandibular hypoplasia, skeletal anomalies such as progressive osteolysis of the terminal phalanges and clavicles, and skin changes such as mottled hyperpigmentation and atrophy. The lipodystrophy is characterized by generalized loss of subcutaneous fat involving the face, trunk, and extremities. Some patients have a progeroid appearance. Metabolic complications associated with insulin resistance have been reported (Schrander-Stumpel et al., 1992; summary by Simha et al., 2003). For a general phenotypic description of lipodystrophy associated with mandibuloacral dysplasia, see MADA (248370).

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance, and metabolic abnormalities including insulin resistance and diabetes mellitus. Sensorineural deafness occurs late in the first or second decades of life (summary by Weedon et al., 2013).

Lipodystrophies are rare disorders characterized by loss of body fat from various regions and predisposition to metabolic complications of insulin resistance and lipid abnormalities. FPLD7 is an autosomal dominant disorder with a highly variable phenotype. Additional features, including early-onset cataracts and later onset of spasticity of the lower limbs, have been noted in some patients (summary by Garg et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.

Mandibuloacral dysplasia with type A lipodystrophy (MADA) is an autosomal recessive disorder characterized by growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes. The lipodystrophy is characterized by a marked acral loss of fatty tissue with normal or increased fatty tissue in the neck and trunk. Some patients may show progeroid features. Metabolic complications can arise due to insulin resistance and diabetes (Young et al., 1971; Simha and Garg, 2002; summary by Garavelli et al., 2009). See also MAD type B (MADB; 608612), which is caused by mutation in the ZMPSTE24 gene (606480).

Congenital generalized lipodystrophy type 5 (CGL5) is an autosomal recessive metabolic disorder characterized by childhood onset of lipodystrophy, severe nonalcoholic fatty liver disease, dyslipidemia, hypertriglyceridemia, low HDL, and insulin-resistant diabetes mellitus. Affected individuals also have short stature (Payne et al., 2014). For a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).