Cartilage-hair hypoplasia

Cartilage-hair hypoplasia (CHH), also known as metaphyseal chondrodysplasia, McKusick type, is a rare autosomal recessive skeletal dysplasia caused by mutations in the RMRP gene, which encodes the RNA component of the mitochondrial RNA-processing endoribonuclease complex. The condition was first described in the Old Order Amish population but occurs worldwide. CHH is characterized by short-limbed short stature (dwarfism) that is evident at birth, with disproportionately short limbs relative to the trunk. The skeletal abnormalities result from defective cartilage growth, particularly at the metaphyses of long bones. Fine, sparse, light-colored hair with reduced diameter is a hallmark feature, though hair findings can vary in severity. Beyond the skeletal and hair manifestations, CHH affects multiple body systems. A significant proportion of patients have immune deficiency ranging from mild to severe combined immunodeficiency, which increases susceptibility to infections, particularly viral infections such as varicella. Affected individuals also have an increased risk of malignancies, especially non-Hodgkin lymphoma and other cancers, as well as basal cell carcinoma. Additional features may include macrocytic anemia or other hematologic abnormalities, Hirschsprung disease, and impaired spermatogenesis in males. Joint hypermobility, particularly of the hands, and ligamentous laxity are common. Treatment of CHH is largely supportive and symptom-directed. Growth hormone therapy has been used with limited benefit. For patients with severe combined immunodeficiency, hematopoietic stem cell transplantation (HSCT) may be considered and can correct the immunological defects. Immunoglobulin replacement therapy may be used for antibody deficiency. Regular monitoring for malignancies and infections is essential. Orthopedic interventions may be needed for skeletal complications such as leg bowing. Prognosis varies widely depending on the severity of immune dysfunction, with some patients having a near-normal lifespan while others face life-threatening complications from infections or malignancy.

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