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.

All About Genetics

What do you know about your family tree? Have any of your relatives had health problems that tend to run in families? Which of these problems affected your parents or grandparents? Which ones affect you or your brothers or sisters now? Which problems might you pass on to your children?

Thanks to advances in medical research, doctors now have the tools to understand much about how certain illnesses, or increased risks for certain illnesses, pass from generation to generation. Here are some basics about genetics.

Genes and Chromosomes

Each of us has a unique set of chemical blueprints affecting how our body looks and functions. These blueprints are contained in our DNA (deoxyribonucleic acid), long, spiral-shaped molecules found inside every cell. DNA carries the codes for genetic information and is made of linked pieces (or subunits) called nucleotides. Each nucleotide contains a phosphate molecule, a sugar molecule (deoxyribose), and one of four so-called "coding" molecules called bases (adenine, guanine, cytosine, or thymidine). The order (or sequence) of these four bases determines each genetic code.

The segments of DNA that contain the instructions for making specific body proteins are called genes. Scientists believe that human DNA carries about 25,000 protein-coding genes. Each gene may be thought of as a "recipe" you'd find in cookbook. Some are recipes for creating physical features, like brown eyes or curly hair. Others are recipes to tell the body how to produce important chemicals called enzymes (which help control the chemical reactions in the body).

Along the segments of our DNA, genes are neatly packaged within structures called chromosomes. Every human cell contains 46 chromosomes, arranged as 23 pairs (called autosomes), with one member of each pair inherited from each parent at the time of conception. After conception (when a sperm cell and an egg come together to make a baby), the chromosomes duplicate again and again to pass on the same genetic information to each new cell in the developing child. Twenty-two autosomes are the same in males and females. In addition, females have two X chromosomes and males have one X and one Y chromosome. The X and the Y are known as sex chromosomes.

Human chromosomes are large enough to be seen with a high-powered microscope, and the 23 pairs can be identified according to differences in their size, shape, and the way they pick up special laboratory dyes.

Genetic Problems

Errors in the genetic code or "gene recipe" can happen in a variety of ways. Sometimes information is missing from the code, other times codes have too much information, or have information that's in the wrong order.

These errors can be big (for example, if a recipe is missing many ingredients — or all of them) or small (if just one ingredient is missing). But regardless of whether the error is big or small, the outcome can be significant and cause a person to have a disability or at risk of a shortened life span.

Abnormal Numbers of Chromosomes

When a mistake occurs as a cell is dividing, it can cause an error in the number of chromosomes a person has. The developing embryo then grows from cells that have either too many chromosomes or not enough.

In trisomy, for example, there are three copies of one particular chromosome instead of the normal two (one from each parent). Trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) are examples of this type of genetic problem.

Trisomy 18 affects 1 out of every 7,500 births. Children with this syndrome have a low birth weight and a small head, mouth, and jaw. Their hands typically form clenched fists with fingers that overlap. They also might have birth defects involving the hips and feet, heart and kidney problems, and intellectual disability (also called mental retardation). Only about 5% of these children are expected to live longer than 1 year.

Trisomy 13 affects 1 out of every 15,000 to 25,000 births. Children with this condition often have cleft lip and palate, extra fingers or toes, foot abnormalities, and many different structural abnormalities of the skull and face. This condition also can cause birth defects of the ribs, heart, abdominal organs, and sex organs. Long-term survival is unlikely but possible.

In monosomy, another form of numerical error, one member of a chromosome pair is missing. So there are too few chromosomes rather than too many. A baby with a missing autosome has little chance of survival. However, a baby with a missing sex chromosome can survive in certain cases. For example, girls with Turner syndrome — who are born with just one X chromosome — can live normal, productive lives as long as they receive medical care for any health problems associated with their condition.

Deletions, Translocations, and Inversions

Sometimes it's not the number of chromosomes that's the problem, but that the chromosomes have something wrong with them, like an extra or missing part. When a part is missing, it's called a deletion (if it's visible under a microscope) and a microdeletion (if it's too tiny to be visible). Microdeletions are so small that they may involve only a few genes on a chromosome.

Some genetic disorders caused by deletions and microdeletions include Wolf-Hirschhorn syndrome (affects chromosome 4), Cri-du-chat syndrome (chromosome 5), DiGeorge syndrome (chromosome 22), and Williams syndrome (chromosome 7).

In translocations (which affect about 1 in every 400 newborns), bits of chromosomes shift from one chromosome to another. Most translocations are "balanced," which means there is no gain or loss of genetic material. But some are "unbalanced," which means there may be too much genetic material in some places and not enough in others. With inversions (which affect about 1 in every 100 newborns), small parts of the DNA code seem to be snipped out, flipped over, and reinserted. Translocations may be either inherited from a parent or happen spontaneously in a child's own chromosomes.

Both balanced translocations and inversions typically cause no malformations or developmental problems in the kids who have them. However, those with either translocations or inversions who wish to become parents may have an increased risk of miscarriage or chromosome abnormalities in their own children. Unbalanced translocations or inversions are associated with developmental and/or physical abnormalities.

Sex Chromosomes

Genetic problems also occur when abnormalities affect the sex chromosomes. Normally, a child will be a male if he inherits one X chromosome from his mother and one Y chromosome from his father. A child will be a female if she inherits a double dose of X (one from each parent) and no Y.

Sometimes, however, children are born with only one sex chromosome (usually a single X) or with an extra X or Y. Girls with Turner syndrome are born with only one X chromosome, whereas boys with Klinefelter syndrome are born with 1 or more extra X chromosomes ( XXY or XXXY).

Sometimes, too, a genetic problem is X-linked, meaning that it is associated with an abnormality carried on the X chromosome. Fragile X syndrome, which causes intellectual disability in boys, is one such disorder. Other diseases that are caused by abnormalities on the X chromosome include hemophilia and Duchenne muscular dystrophy.

Females may be carriers of these diseases, but because they also inherit a normal X chromosome, the effects of the gene change are minimized. Males, on the other hand, only have one X chromosome and are almost always the ones who show the full effects of the X-linked disorder.

Gene Mutations

Some genetic problems are caused by a single gene that is present but altered in some way. Such changes in genes are called mutations. When there is a mutation in a gene, the number and appearance of the chromosomes is usually still normal.

To pinpoint the defective gene, scientists use sophisticated DNA testing techniques. Genetic illnesses caused by a single problem gene include phenylketonuria (PKU), cystic fibrosis, sickle cell disease, Tay-Sachs disease, and achondroplasia (a type of dwarfism).

Although experts used to think that no more than 3% of all human diseases were caused by errors in a single gene, new research shows that this is an underestimate. Within the last few years, scientists have discovered genetic links to many different diseases that weren't originally thought of as genetic, including Parkinson's disease, Alzheimer's disease, heart disease, diabetes, and several different types of cancer. Alterations in these genes are thought to increase one's risk of developing these conditions.

Oncogenes (Cancer-Causing Genes)

Researchers have identified about 50 cancer-causing genes that greatly increase a person's odds of developing cancer. By using sophisticated tests, doctors may be able to identify who has these genetic mutations, and determine who is at risk.

For example, scientists have determined that colorectal cancer is sometimes associated with mutations in a gene called APC. They've also discovered that abnormalities in the BRCA1 and BRCA2 gene give women a 50% chance of developing breast cancer and an increased risk for ovarian tumors.

People who are known to have these gene mutations now can be carefully monitored by their doctors. If problems develop, they're more likely to get treated for cancer earlier than if they hadn't known of their risk, and this can increase their odds of survival.

New Discoveries, Better Care

Scientists have made major strides in the field of genetics over the last two decades. The mapping of the human genome and the discovery of many disease-causing genes has led to a better understanding of the human body. This has enabled doctors to provide better care to their patients and to increase the quality of life for people (and their families) living with genetic conditions.

Reviewed by: Nina Powell-Hamilton, MD
Date reviewed: September 26, 2016