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Cartilage Hair Hypoplasia

Mckusick's Metaphyseal Chondrodysplasia Syndrome

Cartilage hair hypoplasia is a rare multisystemic genetic disorder demarcated by a short stature from birth, hypoplastic hair, various skeletal abnormalities and a variable degree of immunodeficiency that can be fatal in the absence of an early diagnosis. Clinical signs, results from imaging studies, and genetic testing are necessary parts of the diagnostic workup.


Signs and symptoms of cartilage hair hypoplasia (CHH) may be evident from birth, when disproportionately short limbs, considered as a cardinal feature of CHH, are identified [1] [2]. Consequently, a short stature is evident in all patients, with metaphyseal dysplasia being the principal pathological event [2] [3]. Bowing of the lower extremities, a prominent reduction in the length of the tibia compared to the fibula, very short hands characterized by increased laxity of the metacarpal, interphalangeal and phalangeal joints, and incomplete extension of the elbow joint are important additional skeletal manifestations of CHH [2] [3]. Apart from growth abnormalities, the appearance of a fine, light-colored and sparse, short hair is the second main component of the clinical presentation [2]. Hypopigmentation of the skin and nail dysplasia can be identified in some cases [4]. Immunodysfunction, humoral and/or cell-mediated, is readily observed, ranging from mild subclinical forms to severe combined immunodeficiency (SCID) [2] [3]. In fact, neutropenia and lymphopenia frequently create favorable conditions for recurrent infections, seen in up to 60% of patients, and are the principal causes of death in CHH [3]. Gastrointestinal conditions, such as malabsorption, celiac disease or Hirschsprung's disease are identified in about 18% of cases, which may be one of the contributing factors for failure of infants to thrive throughout childhood, another possible symptom [4]. Finally, immunodeficiency combined with anemia that is commonly noted shows a significant predilection toward hematologic malignancies, especially lymphomas [2] [3].

  • Skin should be inspected for abnormal changes, lymph nodes for enlargement, and abdomen for hepatomegaly, splenomegaly, or other abnormalities.[ncbi.nlm.nih.gov]
Short Stature
  • We conclude that recessive metaphyseal dysplasia without hypotrichosis is a variant of CHH, manifesting only as short stature and metaphyseal dysplasia.[ncbi.nlm.nih.gov]
  • Imaging studies are used to distinguish CHH from numerous other causes of short stature.[symptoma.com]
  • Anemia is seen in over 80% of patients with cartilage-hair hypoplasia (CHH). While this is usually mild and self-limited, some patients demonstrate a severe, persistent anemia resembling that seen in Diamond-Blackfan anemia (DBA).[ncbi.nlm.nih.gov]
  • Finally, immunodeficiency combined with anemia that is commonly noted shows a significant predilection toward hematologic malignancies, especially lymphomas.[symptoma.com]
Hodgkin Lymphoma
  • CONCLUSIONS: This study confirms an increased risk of cancer, especially non-Hodgkin's lymphoma, probably attributable to defective immunity, among patients with CHH.[ncbi.nlm.nih.gov]
  • Thus the SMR for non-Hodgkin's lymphoma alone would be approximately 80. In addition, there were two accidental deaths (ages 42 and 24 years; SMR 3.8, 95% CI 0.5 to 14).[adc.bmj.com]
  • The most common cancers are non-Hodgkin lymphoma, squamous cell carcinoma, leukemia, and Hodgkin lymphoma. The reason why individuals with McKusick type metaphyseal chondrodysplasia have increased risks for cancer is unclear at this time.[rarediseases.org]
Recurrent Infection
  • In fact, neutropenia and lymphopenia frequently create favorable conditions for recurrent infections, seen in up to 60% of patients, and are the principal causes of death in CHH.[symptoma.com]
  • It is characterized by disproportionate short stature, fine sparse hair, ligamentous laxity, hematological abnormalities with anemia, a predisposition to malignant tumors, and recurrent infections usually due to cellular and/or humoral immunodeficiency[ncbi.nlm.nih.gov]
Weight Gain
  • .  Treatment :  Caution regarding weight gain  Treat limb alignment and perform early joint replacement  Shelf acetabular augmentation in some patients - to improve coverage of the misshapen femoral head  Osteotomies may be helpful in realigning[slideshare.net]
Failure to Thrive
  • We report on a Thai girl who first presented with chronic diarrhea, recurrent pneumonia, and severe failure to thrive, without apparently disproportionate dwarfism.[ncbi.nlm.nih.gov]
  • . - Gastrointestinal dysfunction: This can present with signs of malabsorption, diarrhea, celiac disease, and failure to thrive. This requires symptomatic treatment.[atlasgeneticsoncology.org]
  • Intestinal malabsorption presents as diarrhea, and decreased ability to gain weight (failure to thrive) in the newborn period. Most of the intestinal symptoms appear within the first two years of life.[rarediseases.org]
  • Indeed, in patient 1 and 2 the diagnosis of CHH was delayed until after failure to thrive (body weight) but not linear growth was reversed after reconstitution of the immune system with BMT.[nature.com]
Hair Hypoplasia
  • Irwin GAL (1966) Cartilage-hair hypoplasia (CHH) Variant of familial metaphyseal dysostosis. Radiology 86:926–928 PubMed Google Scholar 12. Kaitila I, Perheentupa J (1980) Cartilage-hair hypoplasia.[doi.org]
  • Diverse autoantibody reactivity in cartilage-hair hypoplasia.[ncbi.nlm.nih.gov]
Sparse Hair
  • Cartilage-hair hypoplasia (CHH) is a rare autosomal-recessive disorder characterized by short-limbed dwarfism, sparse hair, and immune deficiency.[ncbi.nlm.nih.gov]
Skin Lesion
  • We report a child with short stature since birth who was otherwise well, presenting at 2.8 years with progressive granulomatous skin lesions when diagnosed with severe T cell immunodeficiency.[ncbi.nlm.nih.gov]
  • Pre-existing autoimmunity and inflammatory skin lesions were a prominent feature in 5 of 16 patients (patient nos. 3, 5, 8, 11, and 12; Table 1 ). Thirteen patients were transplanted in early childhood (mean age 2.5 years).[bloodjournal.org]
  • This study suggests that Hirschsprung disease is associated especially with severe cartilage-hair hypoplasia: the patients with Hirschsprung disease had severe growth failure and a higher incidence of alopecia, infections, malignancies, and childhood[ncbi.nlm.nih.gov]
  • About 15% of affected individuals have complete hair loss (alopecia), which includes the scalp, eyelashes, eyebrows, and body hair. Decreased red blood cell production (anemia) has been reported in about 80% of affected individuals.[rarediseases.org]
  • Increased ligamentous laxity was present in 95%, limited extension of the elbows in 92%, increased lumbar lordosis in 85%, thoracal deformity in 68%, genu varum in 63% and scoliosis in 21% of the patients.[ncbi.nlm.nih.gov]
  • […] peptide (PTHRP) receptor mental retardation short limbed dwarfism wide eyes monkey like stance ostebulbous metaphyseal expansion of long bones seen on xray Schmid's autosomal dominant defect in Type X collagen short limbed dwarfism excessive lumbar lordosis[orthobullets.com]
Short Hands
  • Other symptoms include short hands and possibly short, deformed limbs (varus). X-ray reveals metaphyseal lesions, especially in the knees, and large, round epiphyses during childhood.[orpha.net]
  • Bowing of the lower extremities, a prominent reduction in the length of the tibia compared to the fibula, very short hands characterized by increased laxity of the metacarpal, interphalangeal and phalangeal joints, and incomplete extension of the elbow[symptoma.com]
Short Arm
  • We have previously mapped the gene for CHH to the short arm of chromosome 9 in Finnish and Amish families. The CHH locus resides close to D9S163 within an interval of 1.5 cM flanked by D9S165 and D9S50.[ncbi.nlm.nih.gov]
  • The locus of the gene has been mapped to the short arm of chromosome 9. Patients with CHH usually suffer from cellular immunodeficiency.[en.wikipedia.org]
  • Signs & Symptoms Unevenly short arms and legs (short limbed dwarfism) are the most common features in McKusick type metaphyseal chondrodysplasia and are seen in around 100% of affected individuals.[rarediseases.org]
  • Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia. Genomics 14, 437–443 (1992). 21 Anderson, M.A. & Gusella, J.F.[doi.org]
  • And a little girl who would grow up to be four feet tall with exceedingly short arms and legs does not fit that paradigm. Seventeen years later, we are on the verge of being able to do something when our image of perfection is threatened.[theguardian.com]
Short Extremities
  • Before birth Possibly via prenatal ultrasound due to short extremities Genetic sampling if expected After birth X-ray findings Observation of common physical characteristics Confirmation by DNA testing of the RMRP gene via a blood test What are the common[littlepeopleuk.org]
  • […] small chest with short ribs Plain radiograph short, bowed femurs with metaphyseal flare and irregularity eleven ribs, moderately short Flared and irregular metaphyses of multiple long bones are also associated with these dysplasias, as well as mild platyspondyly[radiopaedia.org]
  • .  Generalised severe platyspondyly  Increased intervertebral disc height  Open staircase vertebrae  Kyphosis/ scoliosis  Widening sclerosis irregularity of tubular bones  Irregular femoral epiphysis  Retarded bone maturation 17.[slideshare.net]


CHH must be considered in the differential diagnosis of a short stature that appears from birth and accompanying features such as hair hypoplasia and immunodeficiency that predisposes individuals to recurrent infections. For this reason, a meticulously performed physical examination is a pivotal step. Despite the genetic nature of the disorder, its mode of inheritance (autosomal recessive) does not mandate a positive family history, but nevertheless, the appearance of similar signs and symptoms in close relatives or siblings must be noted. Laboratory studies will reveal transient macrocytic anemia, lymphopenia with a decreased CD4+/CD8+ T-cell count, and neutropenia [2] [3]. Imaging studies are used to distinguish CHH from numerous other causes of short stature. Metaphyseal dysplasia seen on X-rays of the limbs is the principal radiologic feature, accompanied by thickening and shortening of the tubular bones (distal femur, proximal tibia and bones of the hands), excessive length of the distal fibula, flaring of the costochondral junction, delayed ossification, and cone-shaped phalangeal epiphyses [3] [4]. If these features are identified during infancy, CHH is a highly likely diagnosis, in which case genetic studies should be pursued to confirm the underlying cause. Sequencing of the mitochondrial RNA-processing (RMRP) gene, the main culprit in the pathogenesis of CHH, located on chromosome 9p13.3 [1] [2], is available and advised whenever valid clinical suspicion exists based on clinical and radiographic criteria.

  • A 29-year-old white woman had short limbs, hyperextendable joints, fine skin and body hair, anergy to common skin test antigens, subnormal lymphocyte response to phytohemagglutinin, and increased numbers of natural killer cells, characteristic of cartilage-hair[ncbi.nlm.nih.gov]
  • CD8 lymphocytopenia was identified as a novel phenotype associated with RMRP mutations. Significant, even intrafamilial, phenotypic heterogeneity was observed.[ncbi.nlm.nih.gov]
  • This could explain at least in part the severe lymphocytopenia in some patients with CHH and the observed low lymphocyte proliferation to specific mitogens in vitro.[bloodjournal.org]


  • After the surgery, we continued GH treatment. Additional GH treatment of 3.6 more years had kept his height to -2.0 SD.[ncbi.nlm.nih.gov]
  • Management and treatment Immunodeficiency, when severe, may require bone marrow transplantation but this does not have any effect on the growth deficiency.[orpha.net]


  • Prognosis The prognosis depends on the presence and severity of the immune deficiency and the possible association with Hirschsprung disease (see this term). The documents contained in this web site are presented for information purposes only.[orpha.net]
  • CONCLUSIONS: HD associated with CHH has poor prognosis in terms of postoperative morbidity and risk of death. These patients require particular attention during postoperative follow-up to detect potentially lethal complications.[ncbi.nlm.nih.gov]


  • The etiology of this finding remains unclear. Some causes of such deposits can be of a reversible nature, thus prompting early recognition although their consequences on clinical outcome remain mostly unknown.[ncbi.nlm.nih.gov]
  • Etiology Mutations in the RMRP (RNA component of mitochondrial RNA-processing endoribonuclease) gene, which maps to the 9p21-p12 locus, are responsible for the disease.[orpha.net]


  • An epidemiological and genetic study of CHH in Finland showed 107 patients, 46 males and 61 females, in 85 families. Eighteen of them had died, seven before the age of 1 year. The living patients ranged in age from 1 to 51 years, median 21 years.[ncbi.nlm.nih.gov]
  • Summary Epidemiology Prevalence is unknown. Clinical description The disease is associated with fine, slow growing hair, and sometimes with immune deficiencies. Other symptoms include short hands and possibly short, deformed limbs (varus).[orpha.net]
Sex distribution
Age distribution


  • PURPOSE OF REVIEW: To report on the expanding clinical and immunological spectrum associated with ribonuclease mitochondrial RNA-processing mutations and to review the cellular and molecular mechanisms involved in the pathophysiology of cartilage-hair[ncbi.nlm.nih.gov]
  • Here, we critically review the underlying genetics in old and new ribosomopathies and examine the pathophysiologic consequences of aberrant ribosome biogenesis.[els.net]
  • Introduction Heterogeneous group of disorders characterized by metaphyseal changes of the tubular bones with normal epiphyses Epidemiology incidence skeletal dysplasias occur at a rate of 2 to 3 newborns per 10,000 births Pathophysiology metaphyseal dysplasia[orthobullets.com]
  • Pathophysiology The genetic defect in cartilage-hair hypoplasia has been identified as a mutation in the gene for RNAase RMRP, mapped to 9p12. [3, 4, 5, 6, 7, 8, 9, 52, 56] RMRP is a ribonucleoprotein present in the nucleus and mitochondria.[emedicine.medscape.com]


  • In this patient, long-term administration of granulocyte colony-stimulating factor increased peripheral neutrophil counts and prevented recurrent hospitalizations for bacterial lower respiratory tract infections.[ncbi.nlm.nih.gov]
  • We strive to maximize children’s mobility, correct deformity, and prevent future complications.[nemours.org]
  • He also suggested regular doctor visits with preventative scans, to ensure that she lives for many years to come.[recapo.com]
  • Hospital for Sick Children Health A-Z Search a complete list of child health articles expand_more View All Drug A-Z Search a list of articles about medications expand_more View All Learning Hubs Browse a complete list of content groups Healthy Living & Prevention[aboutkidshealth.ca]
  • […] after HSCT, whereas only rarely did they reach the age of 30 with best conventional treatment. 25 – 27 Hence, there is great hope that HSCT-associated restoration of normal T-lymphocyte and natural killer (NK)–cell immunity in CHH patients may also prevent[bloodjournal.org]



  1. Horn J, Schlesier M, Warnatz K, et al. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia. Hum Immunol. 2010;71(9):916-919.
  2. Riley P, Weiner DS, Leighley B, et al. Cartilage hair hypoplasia: characteristics and orthopaedic manifestations. J Child Orthop. 2015;9(2):145-152.
  3. Baradaran-Heravi A, Thiel C, Rauch A, Zenker M, Boerkoel CF, Kaitila I. Clinical and Genetic Distinction of Schimke Immuno-Osseous Dysplasia and Cartilage-Hair Hypoplasia. American journal of medical genetics Part A. 2008;146A(15):2013-2017.
  4. Shiasi Arani K. Cartilage Hair Hypoplasia: First report from Iran. Med J Islam Repub Iran. 2013;27(3):157-160.

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Last updated: 2019-07-11 20:29