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cartilage-hair hypoplasia

MIM.250250 9p21-p12

Wednesday 9 February 2005

Definition: Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder characterized by short-limbed skeletal dysplasia.

The skeletal dysplasia cartilage-hair hypoplasia syndrome (CHH) combines metaphyseal dysplasia with short limb dwarfism, fine, sparse and blond hair, transient macrocytic anaemia and immunodeficiency. Hirschsprung disease is associated in approximately 10% of the cases.

Some patients also have defects in cell-mediated immunity and antibody production.

It is associated with germline mutations in the RMRP gene (MIM.157660). The gene mutated in CHH encodes the untranslated RNA component of the mitochondrial RNA-processing ribonuclease (RNAse MRP) and is called RMRP.

Interestingly, Hirschsprung disease has been reported in the Holmgren-Connor syndrome (MIM.211120) which may be allelic to CHH.


- metaphyseal dysplasia
- short limb dwarfism
- fine, sparse and blond hair
- transient macrocytic anaemia
- immunodeficiency
- pediatric systemic granulomatosis

- opportunistic infections


Cartilage-hair hypoplasia (CHH; also known as McKusicktype metaphyseal chondrodysplasia [MIM.250250]) is an autosomal recessive disorder that was first recognized in the Old Order Amish population.

This condition shows an exceptionally high prevalence in Finland, but sporadic cases occur worldwide. CHH is characterized by short-limbed dwarfism, hypoplastic hair growth, ligamentous laxity, and impaired cell-mediated immunity.

An increased risk of cancer has also been reported.

Although a strong genotype/phenotype correlation has been found by means of in vitro testing of different mutations, patients with the same genotype can show very variable degrees of immunodeficiency.

Immunodeficiency in patients with CHH affects predominantly T cell–mediated immunity, but antibody deficiencies have also been described.

An increase in mortality associated with defective immunity has been reported. Other features of CHH include hypoplastic anemia.

Although several groups have reported successful immune reconstitution
after allogeneic hematopoietic stem cell transplantation (HSCT), this therapy does not change the course of skeletal dysplasia.

The effect of HSCTon the increased risk of malignancy remains to be elucidated.


- Hirschsprung disease (12407544)


- germline mutations in the RMRP gene (MIM.157660)

  • The gene RMRP has been mapped to chromosome 9p13.


- Granulomatous inflammation in cartilage-hair hypoplasia: risks and benefits of anti-TNF-α mAbs. Moshous D, Meyts I, Fraitag S, Janssen CE, Debré M, Suarez F, Toelen J, De Boeck K, Roskams T, Deschildre A, Picard C, Bodemer C, Wouters C, Fischer A. J Allergy Clin Immunol. 2011 Oct;128(4):847-53. PMID: 21714993