Inherited disorder with hyperinsulinemia caused by
insulin resistance combined with lipodystrophy and acromegaloid features.
Berardinelli-Seip-Lawrence Syndrome; Berardinelli
Syndrome; Seip Syndrome; Seip-Lawrence Syndrome; Congenital Generalized
Lipodystrophy; (Congenital) Lipoatrophic Diabetes;
Lipodystrophy-Acromegaloid Gigantism Syndrome.
Estimated prevalence is 0.2-0.3:100,000 in
the general population.
Autosomal recessive disorder. Two genetic loci
(11q13 and 9q34) are associated with the syndrome.
No unifying pathogenetic mechanism has been
identified. The insulin receptor seems to be normal.
Based on the clinical picture, including
hyperinsulinemia and in some cases a positive family history.
Berardinelli-Seip syndrome commonly refers to the congenital form of
generalized lipodystrophy, whereas Seip-Lawrence syndrome usually refers to
the acquired form (in which the anabolic syndrome is more variable and
immunologic disturbances more common; see also Other Conditions to Be Considered).
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.
No reports describing anesthesia in
these patients have been published. However, two features require special
attention: diabetes mellitus and cardiovascular involvement. The latter
rarely causes problems in childhood, but the risk of coronary ischemia must be
considered in young adult patients. If in doubt, at least a chest radiograph
and electrocardiogram should be obtained, and chronic cardiac medication must be
evaluated. Abrupt discontinuation of angina pectoris medication can
precipitate an ischemic episode. Assess hepatic and pancreatic function
Management of the metabolic and
cardiovascular derangements follows standard approach. If there are any signs
of coronary heart disease, attention should be paid to provide adequate
sedation and analgesia. Any increase in myocardial oxygen demand should be
avoided (increase in afterload, contractility, or heart rate). Toddlers are
at increased risk for developing ...