Which are the causes of Rabson-Mendenhall Syndrome?

Rabson-Mendenhall Syndrome (RMS) is a rare genetic disorder that is characterized by severe insulin resistance. It was first described by Rabson and Mendenhall in 1956. This syndrome is inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for their child to be affected.

The primary cause of Rabson-Mendenhall Syndrome is mutations in the insulin receptor gene (INSR). The INSR gene provides instructions for making the insulin receptor, a protein that is crucial for the normal functioning of insulin. Insulin is a hormone produced by the pancreas that helps regulate blood sugar levels. It allows cells in the body to take up glucose from the bloodstream and use it for energy.

In individuals with Rabson-Mendenhall Syndrome, the mutations in the INSR gene lead to a dysfunctional insulin receptor. As a result, the receptor is unable to effectively bind to insulin, impairing its ability to transmit signals to the cell. This leads to a condition called insulin resistance, where the body's cells do not respond properly to insulin.

Insulin resistance is a key feature of Rabson-Mendenhall Syndrome. It causes the body to produce excessive amounts of insulin in an attempt to compensate for the lack of response from the cells. However, this compensatory mechanism is ineffective, resulting in persistently high levels of insulin in the blood (hyperinsulinemia).

Hyperinsulinemia can have various detrimental effects on the body. It can disrupt normal growth and development, leading to a characteristic appearance in individuals with Rabson-Mendenhall Syndrome, including a distinctive facial appearance with prominent eyes, a broad nose, and thick lips. Additionally, affected individuals may have dental abnormalities, such as delayed tooth eruption and misalignment.

Rabson-Mendenhall Syndrome can also cause abnormalities in other body systems. These may include acanthosis nigricans, a skin condition characterized by dark, thickened patches, particularly in the neck and armpit areas. It can also lead to abnormalities in the nails, hair, and genitalia. Furthermore, individuals with RMS may experience intellectual disability, delayed motor development, and skeletal abnormalities.

It is important to note that Rabson-Mendenhall Syndrome is a complex disorder, and the severity and specific symptoms can vary among affected individuals. Genetic testing is typically required to confirm the diagnosis, and management involves a multidisciplinary approach to address the various medical, developmental, and psychological aspects of the condition.