Cartilage–hair hypoplasia

Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported in 1965 by McKusick.

Signs and symptoms

• Short limb dwarfism
• very fine thin light hairs and eyebrows
• hyperextensible joints of hand and feet
• abnormalities of spine
• neutropenia
• defective antibody and cell mediated immunity

Genetics

Phytohemagglutinin

CHH is an autosomal recessive inherited disorder. It is a highly pleiotropic disorder. A rarely encountered genetic phenomenon, known as uniparental disomy (a genetic circumstance where a child inherits two copies of a chromosome from one parent, as opposed to one copy from each parent) has also been observed with the disorder.

An association between mutations near or within the ncRNA component of RNase MRP, RMRP, has been identified. The endoribonuclease RNase MRP is a complex of RNA molecule and several proteins and it participates in cleavage of mitochondrial primers responsible for DNA replication and in pre-rRNA processing in the nucleolus. The locus of the gene has been mapped to the short arm of chromosome 9.

Immunodeficiency

Patients with CHH usually suffer from cellular immunodeficiency. In the study of 108 Finnish patients with CHH, there was detected mild to moderate form of lymphopenia, decreased delayed type of hypersensitivity and impaired responses to phytohaemagglutinin. This leads to susceptibility to and, in some more severe cases, mortality from infections early in childhood. There has also been detected combined immunodeficiency in some patients Patients with CHH often have increased predispositions to malignancies.

Diagnosis

Diagnosis of the CHH-AD spectrum disorders is based on clinical findings, characteristic radiographic findings, and in some cases, evidence of immune dysfunction, macrocytic anemia, and/or gastrointestinal problems. If clinical and radiographic findings are inconclusive, identification of biallelic pathogenic variants in RMRP by molecular genetic testing can confirm the diagnosis and allow for family studies.

Radiographic Findings

• Short and thick tubular bones
• Short and bullet-shaped metacarpals and phalanges with cone-shaped epiphyses
• Metaphyseal dysplasia of all tubular bones, most prominent changes at the knees
• Distal metaphyses. Wide, flared, occasionally scalloped with cystic areas; poor ossification with trabeculation
• Epiphyseal changes. Absent or mild in the femoral head
• Vertebral bodies. Normal or mild biconvexity with increased height, lumbar lordosis, reduced widening of interpediculate distance in the lumbar spine

The diagnosis of CHH-AD is established in a proband with the above Suggestive Findings including clinical and characteristic radiographic findings. If clinical and radiographic findings are inconclusive, identification of biallelic pathogenic variants in RMRP by molecular genetic testing can confirm the diagnosis and allow for family studies.

Treatment

In the newborn. Hypoplastic anemia may require repeated blood transfusions; congenital megacolon or Hirschsprung disease may require surgical resection.

In childhood. Surgery may be needed to fuse unstable cervical vertebrae and/or to treat progressive kyphoscoliosis that compromises lung function in AD; corrective osteotomies may be required to treat progressive varus deformity associated with ligament laxity in the knees. Pubertal maturation may be delayed and may require hormonal induction.

For those with immunodeficiency. Treatment of underlying infections based on their type, location, and severity; immediate antiviral treatment with intravenous high-dose acyclovir for varicella; consideration of prophylactic antibiotic therapy and/or immunoglobulin replacement therapy; physiotherapy and acute and long-term medical management for bronchiectasis. Recurrent severe infections and/or the presence of severe combined immunodeficiency (SCID) and/or severely depressed erythropoiesis may warrant bone marrow transplantation.

Malignancies. Treat in the usual manner.

See also

• List of cutaneous conditions
• List of radiographic findings associated with cutaneous conditions

External links

Classification	ICD-10: Q78.8 OMIM: 250250 MeSH: C535916
External resources	Orphanet: 175