SNP Shot: Genomic Insights

Cartilage-hair hypoplasia (CHH) is a genetic condition affecting bone development, leading to short stature, also known as dwarfism. It is characterized by other skeletal issues, fine and sparse hair (hypotrichosis), and a weakened immune system (immune deficiency), increasing susceptibility to recurrent infections.

Individuals with CHH are born with unusually short limbs and overall short stature. They often exhibit malformations in the cartilage near the ends of the long bones of their arms and legs (metaphyseal chondrodysplasia), which impacts bone development. Increased joint flexibility is common in people with CHH, although they may struggle to fully straighten their elbows.

A characteristic feature of CHH is hair that is lighter than that of other family members. This is due to the absence of the central core of each hair strand, which contains some of the pigment responsible for hair color. The missing core also makes the hair thinner, giving it a sparse appearance. In addition, individuals may have unusually light skin (hypopigmentation), misshapen nails, and dental abnormalities.

The severity of immune deficiency in CHH can vary. The most severely affected individuals are diagnosed with severe combined immunodeficiency (SCID). People with SCID have almost no immune protection against bacteria, viruses, and fungi, making them vulnerable to frequent and persistent infections that can be life-threatening. These infections are often caused by opportunistic organisms that typically do not cause illness in individuals with a normal immune system. Most individuals with CHH, even those with milder immune deficiency, experience infections of the respiratory system, ears, and sinuses. Chickenpox (varicella) is particularly dangerous in these individuals. Some people with CHH also develop autoimmune disorders, where the immune system mistakenly attacks the body's own tissues and organs. Furthermore, individuals with CHH have a higher risk of developing certain cancers, including basal cell carcinomas, leukemia, and lymphoma.

Some individuals with CHH may also experience gastrointestinal problems. These can include difficulties absorbing nutrients properly or intolerance to gluten, a protein found in wheat and other grains (celiac disease). Affected individuals may also have Hirschsprung disease, an intestinal disorder causing severe constipation, intestinal blockage, and an enlarged colon. Narrowing of the anus (anal stenosis) or blockage of the esophagus (esophageal atresia) can also occur.

Inheritance:

CHH follows an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must have mutations for the condition to manifest. The parents of an individual with CHH each carry one copy of the mutated gene but usually do not display any signs or symptoms of the condition themselves.