Cartilage-Hair Hypoplasia Clinical Presentation

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: May 15, 2012
 

History

The clinical findings in cartilage hair-hypoplasia (CHH) are outlined below.[13, 15, 16, 17, 10] 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, P carinii, and cytomegalovirus (CMV). 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.[18, 10] Individuals with cartilage hair-hypoplasia are at increased risk for leukemia and lymphoma. Both Hodgkin lymphoma and non-Hodgkin lymphoma have been reported.

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Physical

Abnormal physical findings of cartilage hair-hypoplasia are present at birth.[13, 19] 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
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Causes

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.

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Contributor Information and Disclosures
Author

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, and Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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

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

Disclosure: Nothing to disclose.

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.

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.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

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 Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

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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[33, 34, 35, 36]
Brand(Manufacturer)Manufacturing ProcesspHAdditives (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 ConcentrationsIgA Content (mcg/mL)
Carimune NF



(CSL Behring)



Kistler-Nitschmann fractionation; pH 4, nanofiltration6.4-6.86% solution: 10% sucrose, < 20 mg NaCl/g proteinLyophilized powder 3%, 6%, 9%, 12%Trace
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization5.1-6Sucrose free, contains 5% D-sorbitolLiquid 5%< 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.10.25M glycineReady-for-use liquid 10%37
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation4-4.5Does not contain carbohydrate stabilizers (eg, sucrose, maltose), contains glycineLiquid 10%46
Gammaplex



(Bio Products)



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



(Baxter Bioscience)



Cohn-Oncley fraction II/III; ultrafiltration; pasteurization6.4-7.25% solution: 5% glucose, 0.3% NaClLyophilized 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 6.4-7.25% solution: 0.3% albumin, 2.25% glycine, 2% glucoseLyophilized powder 5%, 10%< 1.6 (5% solution)
Octagam



(Octapharma USA)



Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization5.1-610% maltoseLiquid 5%200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation; pH 4 incubation, trace pepsin, nanofiltration6.6Per gram of IgG: 1.67 g sucrose, < 20 mg NaClLyophilized 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 filtration4.6-5L-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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