Cartilage-hair hypoplasia: A comprehensive review.

Cartilage-hair hypoplasia (CHH) is a rare syndromic inborn error of immunity, caused by variants in the noncoding RNA gene RMRP. The effects of RMRP deficiency are pleiotropic, affecting the ribosomal RNA processing, cell cycle, and gene regulation. Typical clinical manifestations of CHH include chondrodysplasia with short stature, hair hypoplasia, combined immunodeficiency, and anemia. In addition, individuals with CHH have increased prevalence of malignancies, Hirschsprung's disease, and autoimmunity. The only curative option for immunodeficiency or severe anemia in CHH remains hematopoietic stem cell transplantation. This review summarizes 60 years of CHH research, covering genetic aspects, pathogenesis, clinical and laboratory features, as well as diagnostic and management considerations in CHH.