Cartilage-hair hypoplasia Q77.8

Victor McKusick, 1965

Very rare, autosomal recessive inherited special form of chondrodystrophy with a long torso, bell-shaped thorax, short extremities, connective tissue flaccidity and growth disorders with the development of dwarfism. Fine, weakly pigmented, brittle, generally sparsely developed coat on head and body. Short, brittle nails. Disorders of T-cell immunity are found inconsistently (Vakkilainen S et al.2020). These result in atypical pyoderma and granulomatous skin infiltrates. Gastrointestinal problems such as malabsorption and intolerance to gluten can also occur.

Prevalence figures are not available. CHH was first discovered among the Old Order Amish and is widespread in the Finnish population.

Discussed are autosomal recessive inherited mutations of the RMRP gene (RNA component of mitochondrial RNA-processing endoribonuclease), which is localized on chromosome 9p21-p12. The mutation leads to dysfunction of the enzyme RNase MRP, which functions in the cleavage of RNA strands in mitochondrial DNA synthesis and in the cleavage of preribosomal RNA strands.

Associations with mutations in the AGO3 gene have also been described.

Symptoms become evident in infancy and early childhood.

Radiologically detectable are altered metaphyses, especially at the knees, and in childhood large round epiphyses.

The course of the disease varies. Prognosis is determined by the presence and severity of immunodeficiency and by the possible association with Hirschsprung disease.

Micromelia can be detected by malformation ultrasound early in pregnancy, but is not a specific finding. In cases of severe immunodeficiency, a bone marrow transplant may be necessary. The growth disorder is not affected by this.

1. Bonafe L (2002) RMRP gene sequence analysis confirms a cartilage-hair hypoplasia variant with only skeletal manifestations and reveals a high density of single-nucleotide polymorphisms. Clin Genet 61: 146-151
2. Makitie O (2001) Increased mortality in cartilage-hair hypoplasia. Arch Dis Child 84: 65-67
3. Ridanpaa M et al. (2002) Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin o the major 70A-G muatation of untranslated RMPR. Eur J Hum Gent 10: 439-447

4. Vakkilainen S et al.(2020) Immunodeficiency in cartilage-hair hypoplasia: Pathogenesis, clinical course and management. Scand J Immunol 92:e12913.