Lipodystrophy generalized E88.1

Autosomal recessive hereditary clinical picture with generalized, progressive lipatrophy, gigantism, acromegaly, muscle hypertrophy with athletic type already in infancy, hypertrichosis in the face, insulin-resistant hyperglycemia, hypertriglyceridemia and low HDL cholesterol and fatty liver as well as polycystic ovaries and acanthosis nigricans.

So far, 90 different mutations have been detected in 332 cases. Some mutations were homogeneously distributed and others were specific to geographical regions. Type 2 BSCL was the most frequently reported in the literature (50.3% of cases), followed by type 1 (38.0%), type 4 (10.2%) and type 3 (1.5%). The mutations included frameshift (34.4%), nonsense (26.6%) and missense (21.1%) mutations.

Autosomal recessive mutations of the BSCL1 gene (Berardinelli-Seip congenital lipodystrophy-1 gene; gene locus: 9q34.3) and the BSCL 2 gene (Berardinelli-Seip congenital lipodystrophy-2 gene; Seipin; gene locus: 11q13) are confirmed. Genetic variations in the genes CAV1 and CAVIN1 are also detectable (Craveiro Sarmento AS et al. 2019).

So far, 2 mutated proteins have been found. The function of one protein is unknown. The other protein acts as an enzyme involved in the synthesis of triglycerides and phospholipids.

Integument:

• Hyperpigmentation; hypertrichosis, curly hair, progressive generalized lipodystrophy (from birth, in the absence of adipose tissue, the muscle relief becomes more prominent).
• Extracutaneous manifestations (already detectable in early childhood):
• Macrosomia of the infant and toddler
• Muscle hypertrophy
• athletic (pseudoathletic) aspect already in infancy
• possibly hypertrophic cardiomyopathy.

Later clinical signs:

• acromegaloid tall stature with large hands, feet and ears
• acanthosis nigricans
• marked sexual precocity
• oligomenorrhea
• polycystic ovaries with signs of virilization
• retardation of mental development in approx. 50% of cases
• hyperlipidemia
• insulin-resistant diabetes mellitus with hypertriglyceridemia, low HDL cholesterol and development of fatty liver.

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2. Craveiro Sarmento AS et al. (2019) The worldwide mutational landscape of Berardinelli-Seip congenital lipodystrophy. Mutate Res 781:30-52.
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