Cartilage Hair Hypoplasia

Bone Dysplasia Clinic

Cartilage Hair Hypoplasia

Cartilage Hair Hypoplasia (CHH) was first described among the Old Order Amish by Victor McKusick, and so is also known as Metaphyseal Dysplasia, type McKusick. Although pan-ethnic in distribution, it is quite rare in the general population (probably around 1 in 200,000). It is far more common among the Amish (~1/1500) and Finns (~1/20,000). Although its name emphasizes its effects on cartilaginous bone and on hair development, the most serious medical problems are related to bone marrow and immune function.

Diagnosis has historically been made on the basis of clinical and radiological findings. Clinical characteristics include fine and sparse hair, small stature with disproportionately short limbs and joint laxity. Radiologic features include metaphyseal abnormalities most marked at the knee and moderate to marked hand involvement with coning and metaphyseal abnormalities as well as shortening of the small bones of the hands. More recently, diagnosis has been made using molecular testing, especially in those patients without typical radiological features. In fact, it some have recommended molecular testing for CHH in any patient with severe immunodeficiency and short stature. It appears that bone growth and immune competence are affected by two different functions of the gene causing this disorder and so severity of bone issues or immune dysfunction are not predictive of the other.

Medical Issues and Parental Concerns to be anticipated

Life Expectancy

  • Expectations: Although no life tables have been generated, it is likely that life expectancy is on average diminished because of two primary concerns – overwhelming infections in infancy and malignancy in adolescence and young adulthood.  Nonetheless, clearly some individuals live into old age.


  • Expectations: Intrauterine growth retardation is usually present. There is further fall off of growth velocity in the 1st and 2nd years of life. There appears to be no substantial pubertal growth spurt. These characteristics, together, usually result in moderate to marked short stature; ultimate adult height is typically between 4’0” and 4’4”, although occasional individuals will be up to 5’0” tall. The origin of this marked variability is unknown.
  • Monitoring: Monitor growth to insure normal or near normal growth velocity. No diagnosis-specific growth standards are available.
  • Intervention: Growth hormone has been used occasionally and seems to have some limited benefit. Limb lengthening in adolescence is a possibility and has been successfully carried out in a very few affected individuals.


  • Expectations: No central nervous system abnormalities have been recognized. Cognitive development is normal.  Variations in developmental patterns are to be expected because of short stature, joint laxity, orthopedic complications etc.
  • Intervention: None

Varus Deformity

  • Expectations: Leg alignment abnormalities are common. Most often this is bowing of the lower legs associated with fibular overgrowth. This is sufficiently severe to require surgery in around 15% of affected individuals. Less often, valgus deformity (knock-knees) is present.
  • Monitoring: This requires clinical monitoring throughout childhood. Orthopedic assessment should be sought if varus is severe and, particularly, if it results in pain, decreased activity, decreased walking endurance etc.
  • Intervention: Surgery is appropriate if the varus results in instability, non-remitting pain, marked abnormality of gait etc. Surgical correction typically is by proximal tibial osteotomy (with either internal or external fixation).

Joint Laxity

  • Expectations: Most joints are hypermobile. This is particularly true in the hands and wrists. The one exception is the elbows, in which limitation of movement is typical.
  • Monitoring: Severity of laxity should be periodically assessed. In those with marked instability of the wrists or intrinsic hand joints, fine motor functions may be particularly fatiguing.
  • Intervention: If excess fatigability is noted, interventions to consider include assignment modification in school, using of a stabilizing brace when doing fine motor tasks, early introduction of keyboarding to replace hand-writing etc.

Cervical Spine

  • Expectations: Atlantoaxial instability is found in a small minority of affected individuals – certainly less than 10%.
  • Monitoring: Lateral flexion, neutral and extension cervical spine radiographs should be obtained at the time of first diagnosis, at school entry and then every 5 years until adulthood. Symptoms or signs of cervical myelopathy should be sought with each medical assessment, and, if problems are suspected, then multiposition cervical magnetic resonance imaging is needed.
  • Intervention: In those rare instances in which symptomatic instability is present, posterior cervical fusion should be done.


  • Expectations: Some scoliosis develops in around 20% of affected individuals. However, only infrequently is it sufficiently severe to require intervention.
  • Monitoring: Clinical evaluation for scoliosis should be done yearly to maturity. If a more than trivial curve is noted, this should be assessed radiologically
  • Intervention: Usually no treatment is needed. Curves of more than around 25° should be evaluated by a pediatric orthopedist. Occasional individuals will require bracing; rare individuals may require surgical fusion.


  • Expectations: Hair is usually both of very fine caliber (resulting in ‘silky’ character) and sparse. It is usually less pigmented than would be expected in a given family. While scalp hair character is most often recognized, body hair is also sparse. Less than 10% of affected individuals have normal hair.
  • Monitoring: None
  • Intervention: In some, use of agents to thicken and condition the hair or use of a wig may be warranted.

Immune Function, general

  • Expectations: Abnormalities of immune function are almost uniformly present – more than 95% have some demonstrable abnormality by laboratory testing – but in some there are no clinical manifestations. The most common pattern is T-cell based abnormalities and resultant cellular immune dysfunction. However, humoral immune abnormalities have been reported.  In some there is also lymphopenia (60%) and/or neutropenia. Decreased levels of IgG and IgA are sometimes found (in about 20%). In a small number (less than 5%) severe combined immune-deficiency is present. The character and severity of immunodeficiency may change over time. Around 50-60% of individuals appear to be prone to recurrent and serious infections. Particular vulnerability is present in those less than 2 y of age. In young children bacterial pneumonia is the leading cause of death, with most life-threatening events occurring in the first 12 months of life.
  • Monitoring: All affected individuals should have referral to a clinical immunologist, should be assessed at least yearly for the first 4-6 years, and should have assessment including at least CBC and differential, T-cell subset assessment, mitogen stimulation testing and quantitative immunoglobulins. In those with normal or near-normal immune function testing, yearly reassessment after around 6 years of age is probably unneeded, and repeat laboratory evaluations could be completed every 2-4 years thereafter including in adulthood.
  • Intervention: Aggressive treatment of infections is essential in those with immune dysfunction. Live vaccines probably should not be administered (although in those with truly normal immune screening they probably are safe), but other vaccines are safe and should be used. Depending on the immune dysfunction of patients, different interventions may be warranted for managing immune issues including prophylactic antibiotics, IV immunoglobulin, or/and bone marrow transplantation.

Of special note is Varicella infection. Some individuals seem to have special susceptibility to varicella.  A few persons with cartilage hair hypoplasia have had a lethal course when infected. How common such special susceptibility might be is unknown. Affected children should not have varicella vaccination. Varicella exposure should be avoided as much as possible. If clearly exposed, varicella immune globulin should be administered. If infection occurs, it is appropriate to administer Acyclovir as well.

Autoimmune Disorders

  • Expectations: There is an increased risk of autoimmune abnormalities of all sorts, including, for example, granulomatous inflammation, hemolytic anemia, and thyroid dysfunction.
  • Monitoring: Physicians caring for adults with this disorder need to have a high level of suspicion regarding signs or symptoms suggestive of possible autoimmune disorders.
  • Intervention: Management is the same as in those without CHH.

Immune Function, bronchiectasis

  • Expectations: In those with significant impairment of immunity, diffuse plasmocytic bronchiolitis and progressive bronchiectasis may develop.
  • Monitoring: In any with a history of recurrent pulmonary infections, pulmonary function testing should be done beginning at around 5-7 y of age. In those in whom chronic cough, dyspnea or other worrisome symptoms develop, high resolution CT scan of the chest allows for confirmation of bronchiectasis.
  • Intervention: Aggressive treatment of pulmonary infections is essential in those with immune dysfunction. If bronchiectasis is diagnosed or suspected the help of a pediatric pulmonologist should be sought.


  • Expectations: About 80% of those with this diagnosis have some anemia. It is typically macrocytic and thus easily distinguished from iron deficiency anemia. Clinically significant anemia occurs in around 15% and severe, potentially life threatening anemia in about 5%. When present, the severe anemia is usually permanent and results in transfusion dependence.
  • Monitoring: This should be assessed as part of the immunologic workup already summarized.
  • Intervention: Those with clinically significant anemia should be referred to a pediatric hematologist. Those with severe anemia will require periodic transfusions and subsequent iron chelation. Bone marrow transplantation might be considered for intractable anemia.


  • Expectations: Lifetime malignancy risk is substantial (probably at least 10-15%). Overall risk is around 7 times greater than the regular population. Three malignancies account for most of the excess risk – non-Hodgkins lymphoma (90-fold excess risk), basal cell carcinoma (30-fold excess risk), and squamous cell carcinoma of the skin. Most malignancies that have been reported have been in individuals between 15 y and 45 y of age.
  • Monitoring: Clinical monitoring including careful skin examination beginning in early adolescence.
  • Intervention: Avoidance of any unnecessary sun exposure. Sunscreen with an SPF greater than 30 is warranted. Otherwise, management is as in others who develop these malignancies.

Megacolon (Hirschsprung disease)

  • Expectations: This is an uncommon complication, arising in, at most, 5-10% of affected individuals. It is only relevant in infancy and early childhood.
  • Monitoring: Clinical awareness that gastrointestinal symptoms such as chronic constipation may be more consequential in those with this disorder.
  • Intervention: Management as in others who develop Hirschsprung disease.


  • Expectations: An unknown small minority of individuals have malabsorption resulting in chronic diarrhea, failure to thrive, etc. Celiac disease has also been reported.
  • Monitoring: Clinical awareness.
  • Intervention: Referral to gastroenterologist if needed.

Genetics and Molecular Biology 

Cartilage Hair Hypoplasia appears always to be caused by an autosomal recessive gene abnormality. This means that parents of an affected child will usually have a 25% chance that each subsequent child will be similarly affected. No one else in the family should have significantly increased risk. (About 3-5% of individuals from families with no other affected relatives have uniparental disomy of the region of chromosome 9 that houses the involved gene; in that instance recurrence risk is 0.)

Cartilage Hair Hypoplasia (CHH) is caused by mutations in the RMRP gene.  About 100 different mutations in this gene have been described. RMRP is located on chromosome 9p13.3 and codes for a component of the ribosomal complex (the RNA subunit of the RNase MRP complex); thus, CHH is part of a group of congenital disorders termed ribosomopathies. RMRP is involved in ribosomal assembly, telomere function, and cell cycle control Mutations in the same gene can cause other, related bone dysplasias including a nonspecific metaphyseal dysplasia and anauxetic dysplasia.

Gene testing is warranted if there is diagnostic uncertainty, if the family is concerned about recurrence risk (assessment for uniparental disomy), or if prenatal diagnosis by molecular means is desired. Although there is some genotype-phenotype correlations, this is not yet sufficiently precise to commend gene testing for that purpose.