SNP Shot: Genomic Insights

Donohue syndrome is a rare genetic condition marked by extreme insulin resistance, where the body's cells are unable to effectively use insulin. Insulin's job is to regulate blood sugar by moving glucose from the blood into cells for energy. In Donohue syndrome, severe insulin resistance disrupts blood sugar control and negatively impacts the development and function of various organs and tissues.

The wide range of symptoms in Donohue syndrome stems from this severe insulin resistance. Affected individuals are smaller than normal even before birth, and as infants, they experience failure to thrive, meaning they don't grow or gain weight as expected. Soon after birth, other features appear, including a lack of subcutaneous fat, muscle wasting (atrophy), excessive hair growth (hirsutism), multiple ovarian cysts in females, and enlarged nipples, genitals, kidneys, heart, and other organs. Many also develop acanthosis nigricans, a skin condition causing thickened, dark, velvety patches in skin folds. Characteristic facial features include bulging eyes, thick lips, upturned nostrils, and low-set ears. Infants with Donohue syndrome are prone to frequent, life-threatening infections.

Donohue syndrome belongs to a group of disorders called inherited severe insulin resistance syndromes. These conditions, including Rabson-Mendenhall syndrome and type A insulin resistance syndrome, are related and form a spectrum. Donohue syndrome is the most severe form; most children with this condition don't live past the age of 2.

Inheritance:

Donohue syndrome follows an autosomal recessive inheritance pattern. This means that both copies of the relevant gene in each cell must have mutations for the condition to develop. Individuals with only one copy of the mutated gene are carriers; they usually don't show symptoms of the condition, but each of their children have a chance of inheriting the mutated gene.