Disease group Ectodermal Dysplasia
Synonymous Metaphyseal Chondrodysplasia, McKusick Type
Estimated prevalence -
OMIM 250250
Inheritance Autosomal Recessive
Gene (s) RMRP (157660)


Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive ectodermal dysplasia disorder. Also known as metaphyseal chondrodysplasia, CHH was first identified in 1965 by McKusick et al.1 Patients present with short-limbed dwarfism, sparse hypochromic hair and variable degree of immune dysfunction. Mutations in the gene for RMRP (RNase RMP) have been identified as the molecular basis for this inherited disorder.


Clinical Description

Children born with CHH may be subject to opportunistic infections (affecting 32–56% of patients) due to T and/or B-cell immunodeficiency with a reported increased susceptibility to varicella-zoster infection. Several reports of increased susceptibility to malignancies such as leukaemia and non-Hodgkin's lymphoma have also been documented. Gastrointestinal defects can occur and mayinclude Hirschprung's disease and malabsorption. Varying degrees of anaemia and/or neutropenia may present in childhood which requires careful multidisciplinary management.
Mortality rate is increased due to infections, malignancy (particularly lymphoma at a median age of 33 years, basal cell carcinoma in sun exposed areas) and pulmonary disease (e.g. recurrent respiratory tract infections, bronchiectasis, asthma, interstitial pneumonitis)2,3,4.



In 2001, Ridanpaa et al. reported mutations in the RMRP gene on locus 9p21-p12 as the molecular basis of CHH. RMRP is a ribonucleoprotein required for cell growth and, in 2005, Thiel et al. showed that different RMRP gene mutations led to decreased cell growth by impairing ribosomal assembly and by altering cyclin-dependent cell-cycle regulation.4, 5



Diagnosis is usually made at birth, though the clinical features of short-limbed dwarfism may also be detected in utero. Skeletal radiology is the most useful diagnostic tool and shows shortened long tubular bones, a curved femur with rounded distal epiphyses, anterior angulation of the sternum and short ribs. Flaring of the ribs at the costochondral junction is also a typical feature. Sequencing of genomic DNA for RMRP mutation analysis will help confirm the diagnosis and will aid in genetic counseling.



The mainstay of treatment is the careful monitoring and treatment of symptoms and signs of immunodeficiency and opportunistic infection (especially varicella zoster). Prevention by immunization with pneumococcal and annual influenza vaccines can be recommended.6 Patients should be monitored for lymphopaenia, neutropaenia and anemia - all of which may occur early in infancy. Lymphoma monitoring should also include radiologic evaluation (abdominal ultrasound and other imaging as needed).

Regular screening for further malignancies include dermatologic examination for skin cancer, gynaecologic assessment and cervical cancer screening.

Haematopoietic stem cell transplantation can cure immune dysfunction, but its benefits in mildly symptomatic patients with CHH remain debatable and thus this therapy is indicated primarily in patients with severe combined immunedeficiency or persistent transfusion-dependent anaemia. 

Newborn screening using T cell receptor excision circle (TREC) assay can identify patients with severe T cell deficiency who are at risk for SCID. Absent TREC points towards a greater degree of immunodeficiency and comorbidities (anemia requiring transfusion, Hirschsprung’s disease, failure to thrive) compared to decreased TREC.8




1. McKusick VA, Eldridge R, Hostetler JA, Ruangwit U, Egeland JA. Dwarfism in the Amish II. Cartilage-Hair Hypoplasia. Bull Johns Hopkins Hosp. 1965 May;116:285-326. 

2. Vakkilainen S, Taskinen M, Mäkitie O. Immunodeficiency in cartilage-hair hypoplasia: Pathogenesis, clinical course and management. Scand J Immunol. 2020;92(4):e12913.

3. Scott EM, Chandra S, Li J, Robinette ED, Brown MF, Wenger OK. Abnormal Newborn Screening Follow-up for Severe Combined Immunodeficiency in an Amish Cohort with Cartilage-Hair Hypoplasia. J Clin Immunol. 2020;40(2):321-328.

4. Mäkitie O, Kaitila I. Cartilage-hair hypoplasia--clinical manifestations in 108 Finnish patients. Eur J Pediatr. 1993;152(3):211–7

5. Ridanpaa M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, vanVenrooij W, Pruijn G, Salmela R, Rockas S, et al (2001) Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104:195–20310.1016/S0092-8674(01)00205-7

6. Thiel CT, Horn D, Zabel B, Ekici AB, Salinas K, Gebhart E, Ruschendorf F, Sticht H, Spranger J, Muller D, et al (2005) Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am J Hum Genet 77:795–806

7. Vakkilainen S, Kleino I, Honkanen J, Salo H, Kainulainen L, Gräsbeck M, Kekäläinen E, Mäkitie O, Klemetti P. The Safety and Efficacy of Live Viral Vaccines in Patients With Cartilage-Hair Hypoplasia. Front Immunol. 2020 Aug 11;11:2020

8. Scott EM, Chandra S, Li J, Robinette ED, Brown MF, Wenger OK. Abnormal Newborn Screening Follow-up for Severe Combined Immunodeficiency in an Amish Cohort with Cartilage-Hair Hypoplasia. J Clin Immunol. 2020 Feb;40(2):321-328.