SNP Shot: Genomic Insights

Rabson-Mendenhall syndrome is a rare disease marked by extreme insulin resistance. This means the body's tissues don't respond correctly to insulin, a hormone that normally controls blood sugar. Insulin allows sugar (glucose) to move from the blood into cells for energy. In this syndrome, insulin resistance disrupts blood sugar control, leading to diabetes mellitus, where blood sugar levels become dangerously high.

The severe insulin resistance seen in Rabson-Mendenhall syndrome impacts many areas of development. Affected individuals are smaller than normal even before birth, and infants struggle to thrive, failing to grow and gain weight as expected. Other early signs include a lack of subcutaneous fat (fat under the skin), muscle wasting (atrophy), dental problems, excessive hair growth (hirsutism), multiple ovarian cysts in females, and enlarged nipples, genitals, kidneys, heart, and other organs. Most also develop acanthosis nigricans, a skin condition causing thick, dark, velvety patches in skin folds and creases. Characteristic facial features include prominent, wide-set eyes, a broad nose, and large, low-positioned ears.

Rabson-Mendenhall syndrome is part of a group of related inherited severe insulin resistance syndromes. This group, which also includes Donohue syndrome and type A insulin resistance syndrome, represents a range of severity. Rabson-Mendenhall syndrome falls between Donohue syndrome (usually fatal before age 2) and type A insulin resistance syndrome (often diagnosed in adolescence). Individuals with Rabson-Mendenhall syndrome show symptoms early in life and typically live into their teens or twenties. Death often occurs due to diabetes-related complications, such as diabetic ketoacidosis, a dangerous buildup of acids called ketones.

Inheritance:

This condition follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must have mutations for the condition to develop. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but usually don't exhibit any signs or symptoms of the condition themselves.