Rabson-Mendenhall syndrome

Rabson-Mendenhall syndrome is a rare congenital condition characterized by severe insulin resistance, developmental abnormalities, and acanthosis nigricans. A hypertrophic pineal gland has been reported in some cases.

Clinical Presentation
Rabson and Mendenhall described 3 siblings (2 girls, 1 boy) who initially presented with dental and skin abnormalities, abdominal distention, and phallic enlargement. The children demonstrated early dentition, a coarse, senile-appearing facies, and striking hirsutism. An "adult growth of hair of head" at 5 years of age was pictured in the case of one of the girls. In the older girl the genitalia were large enough at the age of 6 months to permit vaginal examination for diagnosis of a left ovarian tumor which was removed soon afterward. The children were mentally precocious. Prognathism and very thick fingernails as well as acanthosis nigricans were also described. Insulin-resistant diabetes developed, and the patients died during childhood of ketoacidosis and intercurrent infections. At necropsy pineal hyperplasia was found in all three.

Biologically, infants display fasting hypoglycemia, postprandial hyperglycemia and hyperinsulinemia, which progress to permanent hyperglycemia and recurrent diabetic ketoacidosis. The condition is transmitted as an autosomal recessive trait and mainly affects children of consanguineous parents.

Pathophysiology
As in leprechaunism, of which Rabson-Mendenhall syndrome may represent a less severe form, the condition is caused by molecular modification of both alleles of the insulin-receptor gene.

Treatment
Cochran et al. reported that treatment of 2 sibs with Rabson-Mendenhall syndrome with pharmacologic doses of human leptin resulted in improvement of fasting hyperglycemia, hyperinsulinemia, basal glucose, and glucose and insulin tolerance.