Rabson–Mendenhall syndrome is a rare insulin

Insulin

Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 receptor disorder characterized by severe insulin resistance, developmental abnormalities, and acanthosis nigricans

Acanthosis nigricans

Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds, such as the posterior and lateral folds of the neck, the axilla, groin, umbilicus, forehead, and other areas.-Causes:...

. A hypertrophic pineal gland

Pineal gland

The pineal gland is a small endocrine gland in the vertebrate brain. It produces the serotonin derivative melatonin, a hormone that affects the modulation of wake/sleep patterns and seasonal functions...

 has been reported in some cases.

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. The children demonstrated early dentition

Dentition

Dentition pertains to the development of teeth and their arrangement in the mouth. In particular, the characteristic arrangement, kind, and number of teeth in a given species at a given age...

, a coarse, senile-appearing facies, and striking hirsutism

Hirsutism

Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...

. 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

Prognathism

Prognathism is a term used to describe the positional relationship of the mandible and/or maxilla to the skeletal base where either of the jaws protrudes beyond a predetermined imaginary line in the coronal plane of the skull. In general dentistry, oral and maxillofacial surgery and orthodontics...

 and very thick fingernails as well as acanthosis nigricans were also described. Insulin-resistant diabetes

Diabetes mellitus type 2

Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...

 developed, and the patients died during childhood of ketoacidosis

Ketoacidosis

Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies, formed by the breakdown of fatty acids and the deamination of amino acids. The two common ketones produced in humans are acetoacetic acid and β-hydroxybutyrate....

 and intercurrent infections. At autopsy pineal hyperplasia

Hyperplasia

Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....

 was found in all three.

Biologically, infants display fasting hypoglycemia

Hypoglycemia

Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, postprandial hyperglycemia and hyperinsulinemia

Hyperinsulinemia

Hyperinsulinemia, or hyperinsulinaemiais a condition which there is excess levels of insulin circulating in the blood than expected relative to the level of glucose. While it is often mistaken for diabetes or hypoglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and...

, which progress to permanent hyperglycemia and recurrent diabetic ketoacidosis

Diabetic ketoacidosis

Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...

.

Pathophysiology

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

As in leprechaunism, of which Rabson–Mendenhall syndrome represents less severe form, the condition is caused by molecular modification of both allele

Allele

An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

s of the insulin-receptor gene.

Treatment

Treatment of Rabson–Mendenhall syndrome with pharmacologic doses of human leptin

Leptin

Leptin is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones...

may result in improvement of fasting hyperglycemia, hyperinsulinemia, basal glucose, and glucose and insulin tolerance.