Cartilage-Hair Hypoplasia (RMRP)
Cartilage-hair hypoplasia is an autosomal recessive disorder caused by pathogenic variants in the gene RMRP. It has the highest prevalence in the Old Order Amish and Finnish populations. All patients have disproportionately short limbs and stature, and most present with skeletal deformities, joint hypermobility, autoimmune deficiency, and anemia. Rarer symptoms include lymphomas, Hirschsprung disease (characterized by bowel dysmotility), and intestinal malabsorption. Skeletal abnormalities will typically occur prenatally, while patients may develop anemia, immunodeficiencies, or Hirschsprung disease within the first few years of life. The incidence of death in childhood is increased due to autoimmune deficiencies and cancer development, but many patients live into adulthood. There have been no reported genotype-phenotype correlations. As clinical symptoms can vary within a family, it is difficult to predict the severity of the disease based on the inherited variants.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.