Which are the causes of Cartilage-hair hypoplasia (CHH)?

Cartilage-hair hypoplasia (CHH) is a rare genetic disorder that affects the development of cartilage and hair in the body. It is primarily caused by mutations in the RMRP gene, which provides instructions for making a molecule called RNA component of mitochondrial RNA processing endoribonuclease (RNase MRP). This enzyme is involved in the processing of RNA molecules, which are essential for the production of proteins.

The RMRP gene mutations: The mutations in the RMRP gene disrupt the normal functioning of RNase MRP, leading to impaired processing of RNA molecules. This, in turn, affects the production of proteins involved in cartilage and hair development, resulting in the characteristic features of CHH.

Autosomal recessive inheritance: CHH follows an autosomal recessive pattern of inheritance, which means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the disorder. If both parents carry one copy of the mutated gene, they have a 25% chance of having a child with CHH.

Genetic variability: The severity of CHH can vary widely among affected individuals. This is due to the presence of different types of mutations in the RMRP gene, which can result in varying levels of enzyme dysfunction. Some mutations may completely abolish the enzyme's activity, while others may only partially impair its function.

Impaired cartilage development: The primary effect of CHH is the impaired development of cartilage, which is a flexible connective tissue found in various parts of the body, including the skeleton, nose, ears, and trachea. The defective cartilage leads to short stature, skeletal abnormalities, and a weakened immune system.

Abnormal hair growth: Another characteristic feature of CHH is abnormal hair growth. Affected individuals often have sparse, fine, and brittle hair that may be lighter in color. Hair abnormalities can also include alopecia (hair loss) and slow hair growth.

Additional symptoms: In addition to the primary features, CHH can also present with other symptoms such as immune system dysfunction, increased susceptibility to infections, gastrointestinal problems, and an increased risk of certain cancers.

Management and treatment: Currently, there is no cure for CHH, and treatment mainly focuses on managing the symptoms and complications associated with the disorder. This may involve growth hormone therapy to improve stature, immunoglobulin replacement therapy to boost the immune system, and regular monitoring for potential complications.

In conclusion, Cartilage-hair hypoplasia is primarily caused by mutations in the RMRP gene, leading to impaired RNA processing and subsequent abnormalities in cartilage and hair development. The disorder follows an autosomal recessive inheritance pattern and exhibits genetic variability in terms of severity. While there is no cure, appropriate management and treatment can help improve the quality of life for individuals with CHH.