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At a glance

It is an extremely rare inherited condition caused by resistance to insulin with growth deficiency and characterized by dysmorphic facies (“elfin-like”), severe growth retardation, hirsutism, and multiple endocrine disorders. Other features include low birth weight, skin abnormalities (acanthosis nigricans and pachyderma), and significant enlargement of the breast and clitoris in females and the penis in males. Hypertrophic cardiomyopathy has also been observed in these patients.

Synonym

Leprechaunism.

Nature

Endocrine disorder characterized by resistance to insulin caused by abnormal insulin receptors.

History

This medical condition was first described in 1948 by W. L. Donohue (1906-1985), a Canadian pathologist, and I. A. Uchida. They studied two sisters presenting characteristic features that included: cessation of growth at seventh month of gestation, peculiar facies creating a gnome-like appearance, severe endocrine disturbance indicated by emaciation, enlargement of breasts and clitoris, and histologic changes in the ovaries, pancreas and breasts. The name “leprechaunism” has been largely abandoned because of the perception of the name by some parents of patients as insulting.

Incidence

Approximately 50 cases have been reported in the literature. Although the exact incidence has not been established, it is estimated approximately 1:4,000,000 live births.

Genetic inheritance

Inherited as autosomal recessive. The defective gene, which is responsible for encoding of the insulin receptor, has been mapped to 19p13.2. Parental consanguinity is likely for this disorder.

Pathophysiology

The primary defect in leprechaunism is located in the insulin receptor, but a secondary associated defect probably is responsible for growth failure because of an impaired response to endogenous growth hormone. This finding may be explained by the fact that the cytoplasmic subunit of the insulin receptor shares similarities with other receptors that have tyrosine kinase activity (eg, insulin-like growth factor-1, epidermal and platelet-derived growth factor, and certain protooncogenes).

Diagnosis

Clinical aspect and measurement of blood glucose and insulin levels. Prenatal diagnosis is available.

Clinical aspects

The synonym for this syndrome, leprechaunism, is derived from “leprechaun,” the name of a mythical little hairy elf originating from the Irish folklore. Patients have an elfin or gnome-like face with microcephaly, protuberant and low-set ears, large, wide-set eyes, high arched palate, thickened lips, and severely diminished subcutaneous fat (general lipodystrophy) and muscle mass. Skin abnormalities include hypertrichosis (also reflected in the name leprechaun), acanthosis nigricans, and pachyderma. Insulin resistance characterizes the metabolic abnormalities, such as severe hyperinsulinemia, postprandial hyperglycemia, and paradoxical fasting hypoglycemia. Intrauterine and postnatal growth retardation seem to result from a diminished response to growth hormone, at least partially because of downregulation of growth hormone receptors by high insulin levels. The genitalia are enlarged, ...

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