Cartilage Hair Hypoplasia

Cartilage Hair Hypoplasia (CHH) is also known as metaphyseal dysplasia, McKusick type. The disorder was recognized as a clinical entity in 1965, when Victor McKusick and colleagues described the condition in an inbred Amish population (1). The term “metaphyseal” relates to the metaphysis, which is the wide region located at the ends of long bones. The name “Cartilage Hair Hypoplasia” was coined due to the characteristic features: fine, sparse hair and cartilage abnormalities.

How Cartilage Hair Hypoplasia Is Inherited

Cartilage Hair Hypoplasia is typically inherited in an autosomal recessive manner (2).

Causes of Cartilage Hair Hypoplasia

This dysplasia is caused by a mutation of the gene encoding the RNA component of the ribonuclease mitochondrial RNA processing complex (RMRP). The locus of the RMRP gene is on chromosome 9p13. The mutation affects cartilage development.

Physical Characteristics

Cartilage Hair Hypoplasia is a relatively rare congenital disorder. It is most prevalent among the Old-world Amish and Finnish populations. Among Amish people, the incidence is approximately 1.5 in 1000 live births, whereas in Finland, it is 1 in 18,000 to 23,000 (2).

The physical characteristics of Cartilage Hair Hypoplasia include a short limbed form of disproportionate short stature with fine, sparse hair. Intelligence is typically average.

Face and Skull:
  • Relatively average face and skull
  • Fine, sparse, and light hair
  • Sparse eyebrows and eyelashes
Trunk, Chest and Spine:
  • Anterolateral chest deformity
  • Prominent sternum
  • Moderately flared lower rib cage
Arms & Legs:
  • Rhizomelic shortening of the limbs
  • Limited elbow extension, but otherwise ligamentous laxity
  • Short and pudgy hands and feet
  • Possible ankle deformity due to the excessive distal length of
    the fibula
  • Mild bowing of the legs
  • Flat feet
  • Prominent heels
What Are the X-Ray Characteristics?

The major radiographic features in infancy include shortened long tubular bones. The femur is curved with rounded distal epiphyses. Anterior angulation of the sternum and short ribs are also characteristic. The radiographic features in children and adults include short, flared, and irregularly sclerotic metaphyses of tubular bones.

Deformities are more prominent in the knee region than in the proximal femur. A postero-lateral subluxation of the radial head is observed in some patients. The fibula is disproportionately long, most notably at the distal end.

There is minimal craniocaudal widening of interpediculate distance in lumbar spine. Small sagittal and coronal diameters of the vertebrae are typical. Flaring and cupping at the costochondral junction of ribs is also characteristic. The metacarpals and phalanges are severely affected.

Making the Diagnosis

In infancy, diagnosis of Cartilage Hair Hypoplasia is difficult; not until 9 to 12 months of age do the abnormalities become apparent. Radiographic examination provides the greatest insight. Widened metaphyses, short long bones, elongated fibulae, and anterior angulation of the sternum are all indicative of Cartilage Hair Hypoplasia. Hair hypoplasia is only a positive criterion; the absence of hair hypoplasia does not warrant the exclusion of Cartilage Hair Hypoplasia as a possible diagnosis.

Musculoskeletal Problems
Bowing of Legs

Mild bowing of the legs, either genu valgus or genu varum is characteristic and may require corrective osteotomy. Subluxation of the hips may require also surgery. Legg-Perthes disease has been reported in both male and female patients.


Scoliosis is typical of Cartilage Hair Hypoplasia. Depending on the degree of curvature, it can be managed observation, bracing, or surgery.

Problems Elsewhere in the Body
Intestinal Malabsorption

Intestinal malabsorption occurs in approximately 10% of patients. The intestinal malabsorption problem tends to improve on its own.

Hirschsprung Disease

Hirschsprung Disease occurs in approximately 10% of patients. Surgical intervention is oftentimes necessary. Postoperative mortality rates are nearly 40%, due to severe enterocolitis-related septicemia and a compromised immune system.

Humoral Immunity

Humoral immunity is typically compromised. Nearly 56% of younger children experience recurrent infections, especially respiratory tract infections. Children are unusually susceptible to chicken pox. In McKusick’s original study, 6 patients died due to fatal varicella pneumonia. Currently, Acyclovir is most often prescribed to treat the varicella. Patients have a predisposition to cancer, especially non-Hodgkin’s lymphoma and basal cell carcinoma. Again, this susceptibility is due to the compromised T-cell immunity.


Anemia can occur in varying degrees in childhood. In anemic patients, decreased red blood cell proliferation is also observed. Most anemic patients recover spontaneously by adulthood; however fatal hypoplastic anemia can occur in infants. The prevalence of anaemia seems to correlate to the severity of the immunodeficiency and the degree of growth failure.

What to Look for

It is vital to keep a close watch for the possibility of serious infection or malignancy. Varicella and other live virus vaccinations should not be given if the diagnosis is established.

  1. McKusick, V. A.; Eldridge, R.; Hostetler, J. A.; Egeland, J. A.; Ruangwit, U. Dwarfism in the Amish. II. Cartilage-hair hypoplasia. Bull. Johns Hopkins Hosp. 116: 285-326, 1965.
  2. Mäkitie, Outi. Cartilage-Hair Hypoplasia: Clinic radiological and genetic study of an inherited skeletal dysplasia. University of Helsinki, Finland. 1992.

Genetic Testing

Genetic tests are done by analyzing small samples of blood or body tissues. They determine whether you, your partner, or your baby carry genes for certain inherited disorders.

Genetic testing has developed enough so that doctors can often pinpoint missing or defective genes. The type of genetic test needed to make a specific diagnosis depends on the particular illness that a doctor suspects.

Many different types of body fluids and tissues can be used in genetic testing. For deoxyribonucleic acid (DNA) screening, only a very tiny bit of blood, skin, bone, or other tissue is needed.

Genetic Testing During Pregnancy

For genetic testing before birth, pregnant women may decide to undergo amniocentesis or chorionic villus sampling. There is also a blood test available to women to screen for some disorders. If this screening test finds a possible problem, amniocentesis or chorionic villus sampling may be recommended.

Amniocentesis is a test usually performed between weeks 15 and 20 of a woman's pregnancy. The doctor inserts a hollow needle into the woman's abdomen to remove a small amount of amniotic fluid from around the developing fetus. This fluid can be tested to check for genetic problems and to determine the sex of the child. When there's risk of premature birth, amniocentesis may be done to see how far the baby's lungs have matured. Amniocentesis carries a slight risk of inducing a miscarriage.

Chorionic villus sampling (CVS) is usually performed between the 10th and 12th weeks of pregnancy. The doctor removes a small piece of the placenta to check for genetic problems in the fetus. Because chorionic villus sampling is an invasive test, there's a small risk that it can induce a miscarriage.

Why Doctors Recommend Genetic Testing

A doctor may recommend genetic counseling or testing for any of the following reasons:

  • A couple plans to start a family and one of them or a close relative has an inherited illness. Some people are carriers of genes for genetic illnesses, even though they don't show, or manifest, the illness themselves. This happens because some genetic illnesses are recessive — meaning that they're only expressed if a person inherits two copies of the problem gene, one from each parent. Offspring who inherit one problem gene from one parent but a normal gene from the other parent won't have symptoms of a recessive illness but will have a 50% chance of passing the problem gene on to their children.
  • A parent already has one child with a severe birth defect. Not all children who have birth defects have genetic problems. Sometimes, birth defects are caused by exposure to a toxin (poison), infection, or physical trauma before birth. Often, the cause of a birth defect isn't known. Even if a child does have a genetic problem, there's always a chance that it wasn't inherited and that it happened because of some spontaneous error in the child's cells, not the parents' cells.
  • A woman has had two or more miscarriages. Severe chromosome problems in the fetus can sometimes lead to a spontaneous miscarriage. Several miscarriages may point to a genetic problem.
  • A woman has delivered a stillborn child with physical signs of a genetic illness. Many serious genetic illnesses cause specific physical abnormalities that give an affected child a very distinctive appearance.
  • The pregnant woman is over age 34. Chances of having a child with a chromosomal problem (such as trisomy) increase when a pregnant woman is older. Older fathers are at risk to have children with new dominant genetic mutations (those caused by a single genetic defect that hasn't run in the family before).
  • A standard prenatal screening test had an abnormal result. If a screening test indicates a possible genetic problem, genetic testing may be recommended.
  • A child has medical problems that might be genetic. When a child has medical problems involving more than one body system, genetic testing may be recommended to identify the cause and make a diagnosis.
  • A child has medical problems that are recognized as a specific genetic syndrome. Genetic testing is performed to confirm the diagnosis. In some cases, it also might aid in identifying the specific type or severity of a genetic illness, which can help identify the most appropriate treatment.

A Word of Caution

Although advances in genetic testing have improved doctors' ability to diagnose and treat certain illnesses, there are still some limits. Genetic tests can identify a particular problem gene, but can't always predict how severely that gene will affect the person who carries it. In cystic fibrosis, for example, finding a problem gene on chromosome number 7 can't necessarily predict whether a child will have serious lung problems or milder respiratory symptoms.

Also, simply having problem genes is only half the story because many illnesses develop from a mix of high-risk genes and environmental factors. Knowing that you carry high-risk genes may actually be an advantage if it gives you the chance to modify your lifestyle to avoid becoming sick.

As research continues, genes are being identified that put people at risk for illnesses like cancer, heart disease, psychiatric disorders, and many other medical problems. The hope is that someday it will be possible to develop specific types of gene therapy to totally prevent some diseases and illnesses.

Gene therapy is already being studied as a possible way to treat conditions like cystic fibrosis, cancer, and ADA deficiency (an immune deficiency), sickle cell disease, hemophilia, and thalassemia. However, severe complications have occurred in some patients receiving gene therapy, so current research with gene therapy is very carefully controlled.

Although genetic treatments for some conditions may be a long way off, there is still great hope that many more genetic cures will be found. The Human Genome Project, which was completed in 2003, identified and mapped out all of the genes (about 25,000) carried in our human chromosomes. The map is just the start, but it's a very hopeful beginning.

Reviewed by: Larissa Hirsch, MD
Date reviewed: September 26, 2016