Rabson-Mendenhall syndrome

Rabson-Mendenhall syndrome (RMS) is an extremely rare autosomal recessive disorder caused by mutations in the insulin receptor gene (INSR), resulting in severe insulin resistance. It was first described by Rabson and Mendenhall in 1956. The condition belongs to a spectrum of insulin receptor disorders that also includes Donohue syndrome (leprechaunism), which is the most severe form, and type A insulin resistance, which is the mildest. RMS represents an intermediate phenotype on this spectrum. The syndrome profoundly affects multiple body systems. Key clinical features include severe insulin resistance with paradoxical fasting hypoglycemia in early life that progresses to persistent hyperglycemia and diabetic ketoacidosis, intrauterine and postnatal growth retardation, acanthosis nigricans (thickened, darkened skin particularly in body folds), hirsutism (excessive hair growth), abnormalities of the teeth and nails, coarse facial features, pineal gland hyperplasia, and abdominal distension. Affected children often have enlarged genitalia, gingival hyperplasia, and a protuberant abdomen. Patients may also develop features of diabetic complications at a young age due to chronic hyperglycemia. Treatment of Rabson-Mendenhall syndrome is challenging and largely supportive. Management focuses on controlling blood glucose levels, though patients are typically resistant to even very high doses of exogenous insulin. Recombinant human insulin-like growth factor 1 (rhIGF-1, mecasermin) has been used in some patients with variable success to help improve glycemic control. Metformin and other insulin-sensitizing agents may also be tried. Despite treatment, the prognosis remains poor, with many patients succumbing to complications of uncontrolled diabetes, including diabetic ketoacidosis, during childhood or adolescence. Multidisciplinary care involving endocrinology, dermatology, and dental specialists is essential.

Common questions about Rabson-Mendenhall syndrome