cartilagehair

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive skeletal dysplasia characterized by disproportionate short stature due to metaphyseal chondrodysplasia, and fine, sparse scalp hair. The condition occurs worldwide but remains rare, with clinical expression ranging from mild to more pronounced skeletal and immune abnormalities.

Genetics and pathophysiology: CHH is caused by biallelic mutations in the RMRP gene, located on chromosome 11p15.5. RMRP encodes a noncoding RNA involved in ribosomal RNA processing and RNA primer maturation; mutations disrupt cartilage growth and immune system development. Inheritance is autosomal recessive, meaning both parents are typically carriers. The clinical features reflect combined effects on bone growth and immune competence.

Clinical features: In addition to short stature and metaphyseal irregularities, individuals may have bowing of long bones, joint laxity, and distinctive facial features in some cases. Hair is typically sparse and fine. Immune deficiency varies from mild to significant, with recurrent sinopulmonary infections, poor vaccine responses, and sometimes chronic diarrhea. There is an elevated risk of autoimmune disorders and certain malignancies in some patients, particularly related to immune dysfunction.

Diagnosis: CHH is considered based on clinical and radiographic findings and is confirmed by genetic testing for RMRP mutations. Differential diagnosis includes other metaphyseal chondrodysplasias and immunodeficiency syndromes.

Management and prognosis: There is no cure. Management is multidisciplinary and supportive, focusing on growth and skeletal issues (orthopedic care and physical therapy), infection prevention and treatment, appropriate vaccination strategies, and, in selected cases, immunoglobulin replacement therapy. Prognosis depends largely on the severity of immune deficiency and associated complications; many individuals live into adulthood with varying degrees of disability.