Rabson–Mendenhall syndrome

Rabson–Mendenhall syndrome is a rare insulin receptor disorder^[1] characterized by severe insulin resistance, developmental abnormalities, and acanthosis nigricans.^[2] A hypertrophic pineal gland has been reported in some cases.^[3]

Clinical presentation

Rabson and Mendenhall described 3 sibling (2 girls, 1 boy) who initially presented with dental and skin abnormalities, abdominal distention, and phallic enlargement.^[4] 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 autopsy pineal hyperplasia was found in all three.^[4]

Biologically, infants display fasting hypoglycemia, postprandial hyperglycemia and hyperinsulinemia, which progress to permanent hyperglycemia and recurrent diabetic ketoacidosis.

Pathophysiology

Rabson–Mendenhall syndrome has an autosomal recessive pattern of inheritance.

The condition is transmitted as an autosomal recessive trait, and often affects children of consanguineous parents.^[3]

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

Treatment

Treatment of Rabson–Mendenhall syndrome with pharmacologic doses of human leptin may result in improvement of fasting hyperglycemia, hyperinsulinemia, basal glucose, and glucose and insulin tolerance.^[5]

References