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Familial partial lipodystrophy
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Familial partial lipodystrophy

Contributors: Catherine Chung MD, Art Papier MD, Jeffrey D. Bernhard MD, Noah Craft MD, PhD, Lindy P. Fox MD, Lowell A. Goldsmith MD, MPH, Michael D. Tharp MD
Other Resources UpToDate PubMed

Synopsis

The familial partial lipodystrophies are a heterogenous group of disorders with several distinct phenotypes. The most prevalent of these is Dunnigan syndrome, which is characterized by a normal distribution of body fat in childhood with a gradual, progressive lipoatrophy of the upper and lower extremities beginning at puberty, resulting in a muscular appearance. Some patients may gain excess fat in the face and chin as well as neck, leading to a cushingoid appearance. Less commonly, excess fat may also accumulate on the trunk and, in women, in the vulvar area.

Metabolic complications may occur later in life, including diabetes mellitus, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol (HDL), and atherosclerotic disease. These are more common in women with Dunnigan syndrome than in affected men. Fatty liver and acute pancreatitis caused by marked hypertriglyceridemia may also occur. Acanthosis nigricans and polycystic ovarian disease are uncommon associated findings.

Dunnigan-type familial partial lipoatrophy results from an autosomal dominant missense mutation in lamin A/C (LMNA). LMNA encodes two major proteins: lamin A and lamin C. Lamins are intermediate filaments that interact with nuclear envelope proteins, and it is believed that mutations that affect their function lead to lipoatrophy caused by premature adipocyte apoptosis.

While Dunnigan-type familial partial lipodystrophy is the most common type of familial partial lipodystrophy, two additional phenotypes exist. The first is due to an autosomal dominantly inherited mutation in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene; this mutation is associated with a milder phenotype, with the onset of lipodystrophy beginning in the second decade or later in life. Unlike patients with Dunnigan-type lipodystrophy, excess fat deposition in areas such as the face, neck, trunk, and vulva does not occur. In general, patients with PPAR-gamma mutations develop more severe metabolic derangements compared to those with LMNA mutations. The second, mandibuloacral dysplasia, is an extremely rare type of familial partial lipodystrophy. It is inherited in an autosomal recessive fashion. It is characterized by lipodystrophy associated with skeletal abnormalities including hypoplasia of the mandible and clavicle.

Codes

ICD10CM:
E88.1 – Lipodystrophy, not elsewhere classified

SNOMEDCT:
49292002 – Familial partial lipodystrophy

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Last Updated:05/26/2020
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Familial partial lipodystrophy
Familial partial lipodystrophy : Arm, Atrophy, Bilateral distribution, Leg
Clinical image of Familial partial lipodystrophy
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