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Rabson-Mendenhall syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Rabson-Mendenhall syndrome

Rabson-Mendenhall syndrome is a rare, severe insulin resistance disorder that impacts growth, development, and blood sugar regulation.

Overview

Rabson-Mendenhall syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling glucose to be used as energy. In people with Rabson-Mendenhall syndrome, insulin resistance impairs blood glucose regulation and ultimately leads to a condition called diabetes mellitus, in which blood glucose levels can become dangerously high.

Severe insulin resistance in people with Rabson-Mendenhall syndrome affects the development of many parts of the body. Affected individuals are unusually small starting before birth, and infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features of the condition that become apparent early in life include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; dental abnormalities; excessive body hair growth (hirsutism); ovarian cysts in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Rabson-Mendenhall syndrome include prominent, coarse features; a broad nose; and large, low-set ears.

Rabson-Mendenhall syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Rabson-Mendenhall syndrome is intermediate in severity between Donohue syndrome (which is usually fatal before age 2) and type A insulin resistance syndrome (which is often not diagnosed until adolescence). People with Rabson-Mendenhall syndrome develop signs and symptoms early in life and live into their teens or twenties. Death usually results from complications related to diabetes mellitus, such as a toxic buildup of acids called ketones in the body (diabetic ketoacidosis).

Frequency

Rabson-Mendenhall syndrome is estimated to affect less than 1 per million people worldwide. Several dozen cases have been reported in the medical literature.

Causes

Rabson-Mendenhall syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signals that influence many cell functions.

The INSR gene mutations that cause Rabson-Mendenhall syndrome reduce the number of insulin receptors that reach the cell membrane or diminish the function of these receptors. Although insulin is present in the bloodstream, without enough functional receptors it is less able to exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood glucose regulation and affects many aspects of development in people with Rabson-Mendenhall syndrome.

Gene Associated with Rabson-Mendenhall Syndrome

  • INSR

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Frequently Asked Questions

Prognosis hinges on control of hyperglycemia, prevention of severe infections, and management of organ complications (cardiomyopathy, renal disease). Early, aggressive metabolic control and multidisciplinary surveillance can extend survival into adulthood, but many patients experience life‑limiting complications in the second or third decade.
Look for intrauterine growth restriction, failure to thrive despite adequate feeding, marked lack of subcutaneous fat, generalized muscle wasting, and the presence of acanthosis nigricans in skin folds; these signs together with hyperglycemia are red flags for severe insulin resistance syndromes.
Frequent capillary glucose checks (before meals and at bedtime) are essential; many patients require continuous glucose monitoring. Treatment often combines high‑dose insulin (sometimes via insulin pump) with insulin‑sensitizing agents such as metformin or thiazolidinediones, though response is variable and doses must be titrated carefully to avoid hypoglycemia.
Growth hormone therapy has been tried in some cases, but benefits are modest and must be weighed against the risk of worsening insulin resistance. Low‑dose recombinant IGF‑1 can improve glucose utilization and may modestly enhance growth. Management of organ enlargement is mainly supportive—regular cardiac, renal, and hepatic imaging guides timing of interventions such as surgical decompression if organ size compromises function.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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