Cartilage-hair hypoplasia Q77.8

Very rare, autosomal recessive inherited special form of chondrodystrophy with long trunk, bell-shaped thorax, short extremities, slackness of connective tissue, as well as growth disorders with formation of a dwarfism. Fine, weakly pigmented, brittle, altogether sparsely developed coat on head and body. Short, brittle nails. Disorders of T-cell immunity are found inconsistently. This results in atypical pyoderma and granulomatous skin infiltrates.

Prevalence figures are not available.

Autosomal recessive mutations of the RMRP gene (RNA component of mitochondrial RNA-processing endoribonuclease), which is localized on chromosome 9p21-p12, are discussed. 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 pre-ribosomal RNA strands.

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 mutation of untranslated RMPR. Eur J Hum Gent 10: 439-447