Cartilage-hair hypoplasia
Cartilage-hair hypoplasia is a rare genetic disorder characterized by short stature, fine and sparse hair, and immune system deficiencies that can lead to recurrent, life-threatening infections.
Overview & Symptoms
Cartilage-hair hypoplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair; and abnormal immune system function (immune deficiency) that can lead to recurrent infections.
People with cartilage-hair hypoplasia experience a wide range of symptoms affecting multiple body systems:
- Skeletal Abnormalities: Unusually short limbs and short stature from birth. Affected individuals typically have malformations in the cartilage near the ends of the long bones in the arms and legs (metaphyseal chondrodysplasia), which affects bone development. Most individuals are unusually flexible in some joints, but they may have difficulty extending their elbows fully.
- Hair and Skin Features: Hair that is lighter in color than that of other family members because the core of each hair, which contains pigment, is missing. This missing core makes each strand thinner, causing a sparse appearance. Unusually light-colored skin (hypopigmentation), malformed nails, and dental abnormalities may also occur.
- Immune Deficiency: Immune dysfunction ranges from mild to severe. Those with the most severe problems are considered to have severe combined immunodeficiency (SCID), lacking virtually all immune protection and facing repeated, life-threatening infections from opportunistic organisms. Most affected individuals experience infections of the respiratory tract, ears, and sinuses. The chicken pox virus (varicella) often causes dangerous infections. Autoimmune disorders may also occur.
- Increased Cancer Risk: Affected individuals have an increased risk of developing cancer, particularly certain skin cancers, cancer of blood-forming cells (leukemia), and cancer of immune system cells (lymphoma).
- Gastrointestinal Problems: These may include an inability to properly absorb nutrients, gluten intolerance (celiac disease), narrowing of the anus (anal stenosis), blockage of the esophagus, or Hirschsprung disease (an intestinal disorder causing severe constipation, intestinal blockage, and enlargement of the colon).
Frequency
Cartilage-hair hypoplasia occurs most often in the Old Order Amish population, where it affects about 1 in 1,300 newborns. In people of Finnish descent, its incidence is approximately 1 in 20,000. Outside of these populations, the condition is rare, and its specific incidence is unknown. It has been reported in individuals of European and Japanese descent.
Causes
Cartilage-hair hypoplasia is caused by mutations in the RMRP gene. Unlike many genes, the RMRP gene does not contain instructions for making a protein. Instead, a molecule called a noncoding RNA is produced. This RNA binds to several proteins, forming an enzyme complex called mitochondrial RNA-processing endoribonuclease, or RNase MRP.
The RNase MRP enzyme is thought to be involved in several important cellular processes:
- Helping copy (replicate) DNA found in the energy-producing centers of cells (mitochondria).
- Processing ribosomal RNA, which is required for assembling protein building blocks (amino acids) into functioning proteins.
- Controlling the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.
Mutations in the RMRP gene likely result in the production of an unstable noncoding RNA that cannot bind to the proteins needed to make the RNase MRP enzyme complex. This disruption of the enzyme's activity interferes with its vital functions within cells, causing the signs and symptoms of the disorder.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- Cartilage-hair syndrome
- CHH
- McKusick's metaphyseal chondrodysplasia syndrome
- Metaphyseal chondrodysplasia, McKusick type
- Metaphyseal chondrodysplasia, recessive type