Cartilage-Hair Hypoplasia Clinical Presentation

Updated: Aug 06, 2019
  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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The clinical findings in cartilage hair-hypoplasia (CHH) are outlined below. [17, 20, 23, 24, 25, 26] The predominant features include disproportionate short-limbed stature, hair hypoplasia, and immunodeficiency.

The frequencies of reported features are as follows: [1]

  • Short limbed/short stature - 100%
  • Hair hypoplasia - 93%
  • Immunodeficiency in 86% of patients
    • T cell immunodeficiency, 58% in vitro immunodeficiency
    • B cell immunodeficiency, especially specific pneumococcal antibody deficiency
  • Recurrent infections - 56% of patients
    • Varicella most common severe infection
    • Bronchiectasis
  • Hypoplastic childhood anemia - 79%
  • GI dysfunction - 18% ( Hirschsprung disease - 9%)
  • Defective spermatogenesis - 100%
  • Metaphyseal chondrodysplasia - 100%
  • Risk of malignancies - 6.9% ( Non-Hodgkin lymphoma - 90%; basal cell carcinoma - 35%)

Disproportionate short-limbed dwarfism is the most prominent feature in cartilage hair-hypoplasia; it is due to metaphyseal dysplasia. The limbs and ribs are most affected, with sparing of the spine and skull. Radiographic studies reveal short and thick tubular bones, with splaying and irregular metaphyseal borders of the growth plates. The costochondral junctions are similarly affected. These radiographic abnormalities develop by age 6–9 months and are diagnostic.The hair of the scalp, eyebrows and eyelashes  is characteristic in CHH; it is fair, thin, sparse, and white or yellow in color, beginning in the newborn period. In addition, the hair is thinner due to decreased central pigment core core.  In addition, the hair is characteristic in cartilage hair-hypoplasia; it is fair, thin, and sparse, beginning in the newborn period. GI problems occur in approximately 18% of patients with cartilage hair-hypoplasia. Hirschsprung disease is the most common disorder.

Hair of a patient with cartilage-hair hypoplasia ( Hair of a patient with cartilage-hair hypoplasia (left) compared with that of a typical individual. The hair of the patient with cartilage-hair hypoplasia has a smaller diameter because the central pigmented core is absent.

Recently, defective spermatogenesis that affects the number and function of sperm has been identified in all 11 patients with cartilage hair-hypoplasia in one study. Hypoplastic anemia of childhood has been reported in approximately 79% of patients with cartilage hair-hypoplasia and may be life-threatening. It usually resolves by age 2–3 years.

Most individuals with cartilage hair-hypoplasia have limited susceptibility to infections. However, life-threatening varicella infections may occur. Individuals with cartilage hair-hypoplasia occasionally have infections with common pathogens observed in T-cell immunodeficiency, such as Candida species, Pneumocystis carinii, and cytomegalovirus (CMV). In these patients with cartilage hair-hypoplasia, the immunodeficiency may resemble severe combined immunodeficiency (SCID) or Omenn syndrome (OS). [14] OS is characterized as SCID associated with generalized erythroderma, lymphadenopathy, hepatosplenomegaly, and eosinophilia. Individuals with severe combined T- and B-cell immunodeficiency have more serious infections and are susceptible to graft versus host disease.

In some patients with cartilage hair-hypoplasia, a predominant B-cell immunodeficiency with increased susceptibility to bacterial sinopulmonary infections is reported. [17, 27] Toivianen-Salo et al reported that cartilage hair-hypoplasia patients are also at risk of developing bronchiectasis. [28] Autoimmune cytopenia, such as hemolytic anemia and autoimmune neutropenia, and hypothyroidism have also been reported. Moshous et al reported epithelial cell granulomatous lesions in the skin and internal organs of 4 patients with cartilage hair-hypoplasia.

Individuals with cartilage hair-hypoplasia are at increased risk for leukemia and lymphoma. Both Hodgkin lymphoma and non-Hodgkin lymphoma have been reported.



Abnormal physical findings of cartilage hair-hypoplasia are present at birth. [20, 29] Head size is within the normal reference range, hands are short and pudgy, and skin forms redundant folds around the neck and extremities.

Physical findings include the following:

  • Growth - Short-limb dwarfism, average adult height 107–157 cm (40–60 in)

  • Skin - Hypopigmentation

  • Nails - Dysplasia

  • Hair - Fine, sparse, light-colored hair on the scalp, eyebrows, and eyelashes; body hair similarly affected; hair darkens with age. Hair of the scalp, eyebrows, and eyelashes at birth is light in color, fine, and sparse and lacks a central pigmented core.

  • Teeth - Notched incisor, microdontia, doubling of lower premolar lingual cusps

  • Limbs - Short hands, brachydactyly, bowleg

  • Joints - Hypermobility, hyperflexibility, possible limitation of motion affecting elbow extension

  • Spine - Mild platyspondylia, lumbar lordosis

  • Thorax - Flaring of lower rib cage, Harrison grooves

  • GI -Malabsorption, celiac syndrome, Hirschsprung disease, anal stenosis, esophageal atresia



Cartilage-hair hypoplasia is an autosomal recessive inherited disorder. In 2001, mutations of the RMRP gene in the RNA component of the gene for RNase MRP on chromosome band 9p12 were identified as the genetic defect in Finnish patients with cartilage-hair hypoplasia. [6] RNase MRP has 2 functions: (1) cleavage of RNA in mitochondrial DNA synthesis and (2) nucleolar cleaving of pre-rRNA. RMRP mutations have also been identified in three additional syndromes: metaphyseal dysplasia without hypotrichosis (OMIM 250460), kyphomelic dysplasia (OMIM 211350), and anauxetic dysplasia (OMIM 607095). [11, 30, 31]