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

Donohue syndrome

Donohue syndrome is an extremely rare and severe genetic disorder characterized by profound insulin resistance, which severely impacts growth, development, and organ function. It represents the most severe end of the inherited insulin resistance spectrum, with most affected children not surviving past infancy.

Overview

Donohue 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 facilitating the passage of energy (in the form of glucose) from the bloodstream into cells. Severe insulin resistance leads to problems regulating blood glucose levels and affects the development and function of organs and tissues throughout the body.

Donohue syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Rabson-Mendenhall syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Donohue syndrome represents the most severe end of this spectrum; most children with this condition do not survive beyond age 2.

Symptoms and Clinical Features

Severe insulin resistance underlies the varied signs and symptoms of Donohue syndrome, which become apparent starting before birth:

  • Growth Failure: Affected individuals are unusually small starting before birth, and infants experience failure to thrive (faltering weight and growth).
  • Tissue and Muscle Abnormalities: A lack of fatty tissue under the skin (subcutaneous fat) and wasting (atrophy) of muscles.
  • Hormonal and Organ Features: Excessive body hair growth (hirsutism), ovarian cysts in females, and enlargement of the nipples, genitalia, kidneys, heart, and other organs.
  • Skin Changes: A skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety.
  • Facial Features: Distinctive facial features including bulging eyes, thick lips, upturned nostrils, and low-set ears.
  • Infections: Recurrent, life-threatening infections beginning in infancy.

Frequency

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

Causes

Donohue 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 membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.

The mutations that cause Donohue syndrome greatly reduce the number of insulin receptors that reach the cell membrane or disrupt the function of these receptors. Although insulin is present in the bloodstream, without functional receptors it cannot 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.

Associated Gene

  • INSR

Inheritance Pattern

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.

Other Names for This Condition

  • Donohue's syndrome
  • Leprechaunism
  • Leprechaunism syndrome

Frequently Asked Questions

The earliest signs of Donohue syndrome often appear before birth, with infants being unusually small. After birth, key indicators include severe failure to thrive (poor weight gain and growth), a noticeable lack of fatty tissue under the skin, and excessive body hair growth (hirsutism). Parents should seek immediate medical evaluation if their infant exhibits these severe growth and developmental delays, especially combined with unusual skin changes like acanthosis nigricans or enlarged nipples/genitalia, as early diagnosis is crucial for supportive care.
Donohue syndrome is typically diagnosed based on its characteristic clinical features, which include profound insulin resistance, severe growth failure, and distinctive physical abnormalities. Diagnosis is confirmed through genetic testing, which identifies mutations in the INSR gene. Blood tests to measure insulin and glucose levels, along with imaging studies, may also be used to assess organ involvement and overall health.
The primary goals of treatment for Donohue syndrome are to manage severe insulin resistance, support growth and development, and address specific symptoms and complications. This often involves specialized nutritional support to combat failure to thrive, medications to help manage blood sugar levels (though often with limited success due to profound resistance), and multidisciplinary care to address issues like organ enlargement or skin changes. The focus is on providing comfort and maximizing quality of life, as there is currently no cure.
Donohue syndrome is an autosomal recessive genetic disorder, meaning a child must inherit two copies of the mutated INSR gene (one from each parent) to develop the condition. If both parents are carriers of one mutated gene, there is a 25% chance with each pregnancy that their child will be affected, a 50% chance the child will be a carrier, and a 25% chance the child will not be affected and not be a carrier. Genetic counseling is highly recommended for families with a history of Donohue syndrome to understand recurrence risks and discuss options like prenatal diagnosis or preimplantation genetic diagnosis.
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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