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Cartilage-Hair Hypoplasia Clinical Presentation

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
Updated: Jun 08, 2016


The clinical findings in cartilage hair-hypoplasia (CHH) are outlined below.[12, 15, 17, 18, 19] The predominant features include disproportionate short-limbed stature, hair hypoplasia, and immunodeficiency.

The frequency of reported features is as follows[1] :

  • Short limbed/short stature - 100%
  • Hair hypoplasia - 93%
  • Immunodeficiency - 56% (propensity to infections - 58%; in vitro immunodeficiency - 86%)
  • 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. 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.

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).[10] 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.[12, 20] Toivianen-Salo et al reported that cartilage hair-hypoplasia patients are also at risk of developing bronchiectasis.[21] 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.[15, 22] Head size is within the normal reference range, hands are short and pudgy, and skin forms redundant folds around the neck and extremities. Hair of the scalp, eyebrows, and eyelashes at birth is light in color, fine, and sparse and lacks a central pigmented core (see the image below).

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 core is absent.

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
  • 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.[5] RNase MRP has 2 functions: (1) cleavage of RNA in mitochondrial DNA synthesis and (2) nucleolar cleaving of pre-rRNA.

Contributor Information and Disclosures

Alan P Knutsen, MD Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director Jeffrey Modell Diagnostic & Research Center for Primary Immuodeficiences (CGCMC), Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center

Alan P Knutsen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

James M Oleske, MD, MPH François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, Rutgers New Jersey Medical School; Professor, Department of Quantitative Methods, Rutgers New Jersey Medical School

James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of Hospice and Palliative Medicine, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, Pediatric Infectious Diseases Society, Arab Board of Family Medicine, American Academy of Pain Management, National Association of Pediatric Nurse Practitioners, Association of Clinical Researchers and Educators, American Academy of HIV Medicine, American Thoracic Society, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.


John Wilson Georgitis, MD Consulting Staff, Lafayette Allergy Services

John Wilson Georgitis, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Chest Physicians, American Lung Association, American Medical Writers Association, and American Thoracic Society

Disclosure: Nothing to disclose.

  1. Abinun M, Kaitila I, Casanova J-L. Immunodeficiencies with associated manifestations of skin, hair, teeth, and skeleton. Ochs HS, Smith, CIE, Puck JM. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. 2nd ed. New York, NY: Oxford University Press, Inc; 2007. 513-24.

  2. 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. [Medline].

  3. Hermanns P, Tran A, Munivez E, et al. RMRP mutations in cartilage-hair hypoplasia. Am J Med Genet A. 2006 Oct 1. 140(19):2121-30. [Medline].

  4. Thiel CT, Horn D, Zabel B, et al. Severely incapacitating mutations in patients with extreme short stature identify RNA-processing endoribonuclease RMRP as an essential cell growth regulator. Am J Hum Genet. 2005 Nov. 77(5):795-806. [Medline].

  5. Ridanpaa M, van Eenennaam H, Pelin K, et al. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell. 2001 Jan 26. 104(2):195-203. [Medline].

  6. Hirose Y, Nakashima E, Ohashi H, Mochizuki H, Bando Y, Ogata T, et al. Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia. J Hum Genet. July 2011. 51:706-710. [Medline].

  7. Thiel CT, Mortier G, Kaitila I, Reis A, Rauch A. Type and level of RMRP functional impairment predicts phenotype in the cartilage hair hypoplasia-anauxetic dysplasia spectrum. Am J Hum Genet. September 2007. 81:519-529. [Medline].

  8. Ridanpää M, Jain P, McKusick VA, Francomano CA, Kaitila I. The major mutation in the RMRP gene causing CHH among the Amish is the same as that found in most Finnish cases. Am J Med Genet C Semin Med Genet. August 2003. 121:81-83. [Medline].

  9. Ridanpää M, Sistonen P, Rockas S, Rimoin DL, Mäkitie O, Kaitila I. Worldwide mutation spectrum in cartilage-hair hypoplasia: ancient founder origin of the major70A-->G mutation of the untranslated RMRP. Eur J Hum Genet. July 2002. 10:439-447. [Medline].

  10. Notarangelo LD, Roifman CM, Giliani S. Cartilage-hair hypoplasia: molecular basis and heterogeneity of the immunological phenotype. Curr Opin Allergy Clin Immunol. December 2008. 8(6):534-539. [Medline].

  11. Kavadas FD, Giliani S, Gu Y, Mazzolari E, Bates A, Pegoiani E, et al. Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations. J Allergy Clin Immunol. December 2008. 122(6):1178-1184. [Medline].

  12. Makitie O, Kaitila I, Savilahti E. Deficiency of humoral immunity in cartilage-hair hypoplasia. J Pediatr. 2000. 137:487-492.

  13. Joshi AY, Iyer VN, Hagan JB, St Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009. 84(1):16-22. [Medline]. [Full Text].

  14. Makitie O, Marttinen E, Kaitila I. Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients. Pediatr Radiol. 1992. 22(6):434-9. [Medline].

  15. Makitie O, Kaitila I. Cartilage-hair hypoplasia--clinical manifestations in 108 Finnish patients. Eur J Pediatr. 1993 Mar. 152(3):211-7. [Medline].

  16. Buckley RH, Schiff RI, Schiff SE, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997 Mar. 130(3):378-87. [Medline].

  17. Makitie O, Kaitila I, Savilahti E. Susceptibility to infections and in vitro immune function in cartilage-hair hypoplasia. Eur J Pediatr. 1998. 157:816-820.

  18. Makitie O, Pukkala E, Teppo L, Kaitila I. Increased incidence of cancer in patients with cartilage-hair hypoplasia. J Pediatr. 1999 Mar. 134(3):315-8. [Medline].

  19. Makitie O, Kaitila I, Rintala R. Hirschsprung disease associated with severe cartilage-hair hypoplasia. J Pediatr. 2001. 138:929-931.

  20. Ammann RA, Duppenthaler A, Bux J, Aebi C. Granulocyte colony-stimulating factor-responsive chronic neutropenia in cartilage-hair hypoplasia. J Pediatr Hematol Oncol. 2004 Jun. 26(6):379-81. [Medline].

  21. Toivianen-Salo S, Kajosaari M, Piilonen A,Mmakitie O. Patients with cartilage hypoplasia have an increased risk for bronchiectasis. J Pediatr. March 2008. 152:422-428. [Medline].

  22. Makitie O, Kaitila I. Growth in diastrophic dysplasia. J Pediatr. 1997 Apr. 130(4):641-6. [Medline].

  23. Kooijman R, van der Burgt CJ, Weemaes CM, et al. T cell subsets and T cell function in cartilage-hair hypoplasia. Scand J Immunol. 1997 Aug. 46(2):209-15. [Medline].

  24. de la Fuente MA, Recher M, Rider NL, Strauss KA, Morton DH, Adair M, et al. Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. July 2011. 128:139-146. [Medline].

  25. Lux SE, Johnston RB Jr, August CS, et al. Chronic neutropenia and abnormal cellular immunity in cartilage-hair hypoplasia. N Engl J Med. 1970 Jan 29. 282(5):231-6. [Medline].

  26. Williams MS, Ettinger RS, Hermanns P, et al. The natural history of severe anemia in cartilage-hair hypoplasia. Am J Med Genet A. 2005 Sep 15. 138(1):35-40. [Medline].

  27. Glass RB, Tifft CJ. Radiologic changes in infancy in McKusick cartilage hair hypoplasia. Am J Med Genet. 1999 Oct 8. 86(4):312-5. [Medline].

  28. Berthet F, Siegrist CA, Ozsahin H, et al. Bone marrow transplantation in cartilage-hair hypoplasia: correction of the immunodeficiency but not of the chondrodysplasia. Eur J Pediatr. 1996 Apr. 155(4):286-90. [Medline].

  29. Guggenheim R, Somech R, Grunebaum E, Atkinson A, Roifman CM. Bone marrow transplantation for cartilage-hair-hypoplasia. Bone Marrow Transplant. 2006 Dec. 38(11):751-6. [Medline].

  30. Bordon V, Gennery AR, Slatter MA, Vandecruys E, Laureys G, Veys P, et al. Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation. Blood. July 2010. 116(1):27-35. [Medline].

  31. [Guideline] CDC. Update: recommendations from the Advisory Committee on Immunization Practices (ACIP) regarding administration of combination MMRV vaccine. MMWR Morb Mortal Wkly Rep. 2008 Mar 14. 57(10):258-60. [Medline].

  32. Harada D, Yamanaka Y, Ueda K, et al. An effective case of growth hormone treatment on cartilage-hair hypoplasia. Bone. 2005 Feb. 36(2):317-22. [Medline].

  33. Bocca G, Weemaes CM, van der Burgt I, Otten BJ. Growth hormone treatment in cartilage-hair hypoplasia: effects on growth and the immune system. J Pediatr Endocrinol Metab. 2004 Jan. 17(1):47-54. [Medline].

  34. Obara-Moszynska M, Wielanowska W, Rojek A, Wolnik-Brzozowska D, Niedziela M. Treatment of cartilage-hair hypoplasia with recombinant human growth hormone. Pediatr Int. December 2013. 55(6):e162-164. [Medline].

  35. Riley P Jr, Weiner DS, Leighley B, Jonah D, Morton DH, Strauss KA, et al. Cartilage hair hypoplasia: characteristics and orthopaedic manifestations. J Child Orthop. 2015 Apr. 9 (2):145-52. [Medline].

  36. Durandy A, Wahn V, Petteway S, Gelfand EW. Immunoglobulin replacement therapy in primary antibody deficiency diseases - maximizing success. Int Arch Allergy Immunol. 2005. 136:217-229.

  37. Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol. 2008. 122:210-212.

  38. Garcia-Lloret M, McGhee S, Chatila TA. Immunoglobulin replacement therapy in children. Immunol Allergy Clin North Am. 2008 Nov. 28(4):833-49, ix. [Medline]. [Full Text].

  39. Hooper JA. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. 2008 Nov. 28(4):765-78, viii. [Medline].

  40. Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. 2005 Aug 15. 62(16 Suppl 3):S5-11. [Medline].

  41. Siegel J. The Product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy. 2005. 62(11 Pt 2)):78S-84S.

  42. Steer CB, Szer J, Sasadeusz J, et al. Varicella-zoster infection after allogeneic bone marrow transplantation: incidence, risk factors and prevention with low-dose aciclovir and ganciclovir. Bone Marrow Transplant. Mar 2000. 25(6):657-64. [Medline].

  43. Thiel CT. Cartilage-hair-hypolasia-anauexetic dysplasia spectrum disorders. Pagon RA, Bird TD, Dolan CR. Gene Reviews. February 2011.

  44. Huang SW, Ammann AJ, Levy RL, Hong R, Bach FH. Treatment of severe combined immunodeficiency by a small number of pretreated nonmatched marrow cells. Transplantation. 1973 Jan. 15(1):174-6. [Medline].

  45. Makitie O, Pukkala E, Kaitila I. Increased mortality in cartilage-hair hypoplasia. Arch Dis Child. 2001 Jan. 84(1):65-67. [Medline].

  46. Makitie O, Sulisalo T, de la Chapelle A, Kaitila I. Cartilage-hair hypoplasia. J Med Genet. 1995 Jan. 32(1):39-43. [Medline].

  47. Makitie O, Tapanainen PJ, Dunkel L, Siimes MA. Impaired spermatogenesis: an unrecognized feature of cartilage-hair hypoplasia. Ann Med. 2001. 33:201-205.

  48. Moshous D, Meyts I, Fraitag S, Janssen CE, Debré M, Suarez F, et al. Granulomatous inflammation in cartilage-hair hypoplasia: risks and benefitsd of anti-TNF-α mAbs. J Allergy Clin Immunol. October 2011. 128(4):847-853. [Medline].

  49. Polmar SH, Pierce GF. Cartilage hair hypoplasia: immunological aspects and their clinical implications. Clin Immunol Immunopathol. 1986 Jul. 40(1):87-93. [Medline].

  50. Rider NL, Morton DH, Puffenberger E, Hendrickson CL, Robinson DL, Strauss KA. Immunologic and clinical features of 25 Amish patients with RMRP 70 A-->G cartilage hair hypoplasia. Clin Immunol. April 2009. 131:119-128. [Medline].

  51. Sulisalo T, Makitie O, Sistonen P, et al. Uniparental disomy in cartilage-hair hypoplasia. Eur J Hum Genet. 1997 Jan-Feb. 5(1):35-42. [Medline].

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 core is absent.
Table. Immune Globulin, Intravenous [38, 39, 40, 41]
Brand(Manufacturer) Manufacturing Process pH Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs]) Parenteral Form and Final Concentrations IgA Content (mcg/mL)
Carimune NF

(CSL Behring)

Kistler-Nitschmann fractionation; pH 4, nanofiltration 6.4-6.8 6% solution: 10% sucrose, < 20 mg NaCl/g protein Lyophilized powder 3%, 6%, 9%, 12% Trace

(Grifols USA)

Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization 5.1-6 Sucrose free, contains 5% D-sorbitol Liquid 5% < 50
Gammagard Liquid 10%

(Baxter Bioscience)

Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.1 0.25M glycine Ready-for-use liquid 10% 37

(Talecris Biotherapeutics)

Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation 4-4.5 Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycine Liquid 10% 46

(Bio Products)

Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation 4.8-5.1 Contains sorbitol (40 mg/mL); do not administer if fructose intolerant Ready-for-use solution 5% < 10
Iveegam EN

(Baxter Bioscience)

Cohn-Oncley fraction II/III; ultrafiltration; pasteurization 6.4-7.2 5% solution: 5% glucose, 0.3% NaCl Lyophilized powder 5% < 10
Polygam S/D

Gammagard S/D

(Baxter Bioscience for the American Red Cross)

Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated 6.4-7.2 5% solution: 0.3% albumin, 2.25% glycine, 2% glucose Lyophilized powder 5%, 10% < 1.6 (5% solution)

(Octapharma USA)

Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization 5.1-6 10% maltose Liquid 5% 200

(Swiss Red Cross for the American Red Cross)

Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration 6.6 Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl Lyophilized powder 3%, 6%, 9%, 12% 720
Privigen Liquid 10%

(CSL Behring)

Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration 4.6-5 L-proline (~250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose) Ready-for-use liquid 10% < 25
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