2.1. Anauxetic dysplasia

At least four RMRP gene mutations have been identified in people with anauxetic dysplasia, a disorder characterized by severe short stature (dwarfism) and other skeletal abnormalities. The RMRP gene mutations that cause anauxetic dysplasia alter the noncoding RNA produced from the gene, and the RNase MRP enzyme containing the altered noncoding RNA is impaired in its ribosomal RNA processing function. Although the specific mechanism is unknown, impairment of this function likely disrupts skeletal development, leading to the signs and symptoms of anauxetic dysplasia.

2.2. Cartilage-hair hypoplasia

More than 100 mutations that cause cartilage-hair hypoplasia have been identified in the RMRP gene. Approximately 90 percent of cases of this disorder result from a mutation in which the DNA building block (nucleotide) guanine is substituted for the nucleotide adenine at position 70 in the RMRP gene (written as 70A>G). This mutation is found in almost all known affected individuals in the Amish population, approximately 92 percent of affected individuals of Finnish descent, and about half of affected individuals in other populations.

Mutations in the RMRP gene likely result in the production of a noncoding RNA that cannot bind to some of the proteins that are normally part of the RNase MRP enzyme complex. These changes are believed to affect the activity of the enzyme, which interferes with its important functions within cells. Impaired RNase MRP enzyme complex causes dwarfism, skeletal abnormalities, abnormal immune system function (immune deficiency), elevated cancer risk, sparse hair growth (hypotrichosis), and other signs and symptoms of cartilage-hair hypoplasia.

2.3. Other disorders

RMRP gene mutations, including some of the same mutations that cause cartilage-hair hypoplasia (described above), may result in a similar disorder known as metaphyseal dysplasia without hypotrichosis. This condition is characterized by short stature and skeletal abnormalities that are usually less severe than those seen in cartilage-hair hypoplasia. Individuals with metaphyseal dysplasia without hypotrichosis do not have any changes in the structure or appearance of their hair, but they may have immune deficiency and an increased risk of developing cancer. It is unknown why the same mutations may cause both of these conditions. Together with anauxetic dysplasia, they are often referred to as cartilage-hair hypoplasia spectrum disorders, with anauxetic dysplasia as the most severe form and metaphyseal dysplasia without hypertrichosis on the mild end of the spectrum.