Hallmarks of Berardinelli-Seip syndrome are a
near-absent adipose tissue present already at birth or in early infancy and a congenital
(nonketoacidotic) insulin resistance with variable degrees of glucose
intolerance and diabetes mellitus. The insulin resistance with
hyperinsulinemia results in an anabolic syndrome resulting in increased
growth velocity, advanced bone age, muscular hypertrophy and masculine body
build, acromegaloid stigmata, enlarged genitalia in infancy (labial
hypertrophy and sexual precocity, polycystic ovaries), abundant scalp hair
and hypertrichosis, and organomegaly (often with visceral organs showing
twice the normal weight). The anabolic syndrome is further exacerbated by a
voracious appetite. Associated features are liver cirrhosis,
esophageal varices, and hypertriglyceridemia with risk of pancreatitis.
Acanthosis nigricans, which is variable but often marked and extensive,
seems to be a constant sign of Berardinelli-Seip syndrome (as seen in other
syndromes with pronounced insulin resistance). It is most often located in
the extensional areas (elbows, knees) and in places exposed to wear and tear
(axilla, neck, waist). Scoliosis and cystic bone lesions are found in some
patients. Mental retardation is not a constant feature but is present in
approximately 50% of patients. Cardiovascular involvement (arterial
hypertension, hypertrophic cardiomegaly, coronary heart disease) is the
leading cause of early death. Medical management consists of moderate
restriction of caloric intake (preferably with short-chain fatty acids),
insulin as indicated, and antihyperlipidemic drug therapy.