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.
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.
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
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.
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.
Scoliosis is typical of Cartilage Hair Hypoplasia. Depending on the degree of curvature, it can be managed observation, bracing, or surgery.
Intestinal malabsorption occurs in approximately 10% of patients. The intestinal malabsorption problem tends to improve on its own.
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 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.
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.
- 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.
- Mäkitie, Outi. Cartilage-Hair Hypoplasia: Clinic radiological and genetic study of an inherited skeletal dysplasia. University of Helsinki, Finland. 1992.
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Prenatal Genetic Counseling
If you and your partner are newly pregnant, you may be amazed at the number and variety of prenatal tests available to you. Blood tests, urine tests, monthly medical exams, screening tests, and family history tracking — each helps to assess the health of you and your baby, and to predict any potential health risks.
You may also have the option of genetic testing. These tests identify the likelihood of passing certain genetic diseases or disorders (those caused by a defect in the genes — the tiny, DNA-containing units of heredity that determine the characteristics and functioning of the entire body) to your children.
Some of the more familiar genetic disorders are:
- Down syndrome
- cystic fibrosis
- sickle cell disease
- Tay-Sachs disease (a fatal disease affecting the central nervous system)
If your history suggests that genetic testing would be helpful, you may be referred to a genetic counselor. Or, you might decide to seek out genetic counseling yourself.
But what do genetic counselors do, and how can they help your family?
What Is Genetic Counseling?
Genetic counseling is the process of:
- evaluating family history and medical records
- ordering genetic tests
- evaluating the results of this investigation
- helping parents understand and reach decisions about what to do next
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.
Genes are made up of DNA molecules, which are the building blocks of heredity. They're grouped together in specific patterns within a person's chromosomes, forming the unique "blueprint" for every physical and biological characteristic of that person.
Humans have 46 chromosomes, arranged in pairs in every living cell of our bodies. When the egg and sperm join at conception, half of each chromosomal pair is inherited from each parent. This newly formed combination of chromosomes then copies itself again and again during fetal growth and development, passing identical genetic information to each new cell in the growing fetus.
Current science suggests that every human has about 25,000 genes per cell. An error in just one gene (and in some instances, even the alteration of a single piece of DNA) can sometimes be the cause for a serious medical condition.
Some diseases, such as Huntington's disease (a degenerative nerve disease) and Marfan syndrome (a connective tissue disorder), can be inherited from just one parent. But most disorders, including cystic fibrosis, sickle cell anemia, and Tay-Sachs disease, cannot occur unless both the mother and father pass along the gene.
Other genetic conditions, such as Down syndrome, are usually not inherited. In general, they result from an error (mutation) in the cell division process during conception or fetal development. Still others, such as achondroplasia (the most common form of dwarfism), may either be inherited or the result of a genetic mutation.
Genetic tests don't yield easy-to-understand results. They can reveal the presence, absence, or malformation of genes or chromosomes. Deciphering what these complex tests mean is where a genetic counselor comes in.
About Genetic Counselors
Genetic counselors are professionals who have completed a master's program in medical genetics and counseling skills. They then pass a certification exam administered by the American Board of Genetic Counseling.
Genetic counselors can help identify and interpret the risks of an inherited disorder, explain inheritance patterns, suggest testing, and lay out possible scenarios. (They refer you to a doctor or a laboratory for the actual tests.) They will explain the meaning of the medical science involved, provide support, and address any emotional issues raised by the results of the genetic testing.
Who Should See One?
Most couples planning a pregnancy or who are expecting don't need genetic counseling. About 3% of babies are born with birth defects each year, according to the Centers for Disease Control and Prevention (CDC) — and of the malformations that do occur, the most common are also among the most treatable. Cleft palate and clubfoot, two of the more common birth defects, can be surgically repaired, as can many heart malformations.
The best time to seek genetic counseling is before becoming pregnant, when a counselor can help assess your risk factors. But even after you become pregnant, a meeting with a genetic counselor can still be helpful. A genetic counselor can help determine what testing is appropriate for your pregnancy.
Experts recommend that all pregnant women, regardless of age or circumstance, be offered genetic counseling and testing to screen for Down syndrome.
It's especially important to consider genetic counseling if any of the following risk factors apply to you:
- a standard prenatal screening test (such as the alpha fetoprotein test) yields an abnormal result
- an amniocentesis yields an unexpected result (such as a chromosomal defect in the unborn baby)
- either parent or a close relative has an inherited disease or birth defect
- either parent already has children with birth defects, intellectual disabilities, or genetic disorders
- the mother-to-be has had two or more miscarriages or babies that died in infancy
- the mother-to-be will be 35 or older when the baby is born. Chances of having a child with Down syndrome increase with the mother's age: a woman has about a 1 in 350 chance of conceiving a child with Down syndrome at age 35, a 1 in 110 chance at age 40, and a 1 in 30 chance at age 45.
- you are concerned about genetic defects that occur frequently in certain ethnic or racial groups. For example, couples of African descent are most at risk for having a child with sickle cell anemia; couples of central or eastern European Jewish (Ashekenazi), Cajun, or Irish descent may be carriers of Tay-Sachs disease; and couples of Italian, Greek, Middle Eastern, southern Asian, or African descent may carry the gene for thalassemia, a red blood cell disorder.
- either parent is concerned about the effects of exposures they have had to radiation, medications, illegal drugs, infections, or chemicals
Meeting With a Genetic Counselor
Before you meet with a genetic counselor in person, you may be asked to gather information about your family history. The counselor will want to know of any relatives with genetic disorders, multiple miscarriages, and early or unexplained deaths. The counselor will also want to look over your medical records, including any ultrasounds, prenatal test results, past pregnancies, and medications you may have taken before or during pregnancy.
When you meet with the counselor, you'll go over any gaps or potential problem areas in your family or medical history. The counselor can help you understand the inheritance patterns of any potential disorders and help assess your chances of having a child with those disorders.
The counselor will distinguish between risks that every pregnancy faces and risks that you personally face. Even if you discover you have a particular problem gene, science can't always predict the severity of the related disease. For instance, a child with cystic fibrosis can have debilitating lung problems or, less commonly, milder respiratory symptoms.
If more tests are necessary, the counselor will help you set up those appointments and track the paperwork. When the results come in, the counselor will call you with the news and may ask you to come in for another discussion.
Genetic counselors can help you understand your options and adjust to any uncertainties you face, but you and your family will have to decide what to do next.
If you've learned before conception that you and/or your partner are at high risk for having a child with a severe or fatal defect, your options might include:
- pre-implantation diagnosis — when eggs that have been fertilized in vitro (in a laboratory, outside of the womb) are tested for defects at the 8-cell (blastocyst) stage, and only nonaffected blastocysts are implanted in the uterus to establish a pregnancy
- using donor sperm or donor eggs
- taking the risk and having a child
- establishing pregnancy and have specific prenatal testing
If you've received a diagnosis of a severe or fatal defect after conception, your options might include:
- preparing yourself for the challenges you'll face when you have your baby
- fetal surgery to repair the defect before birth (surgery can only be used to treat some defects, such as spina bifida or congenital diaphragmatic hernia, a hole in the diaphragm that can cause severely underdeveloped lungs. Most defects cannot be surgically repaired.)
- ending the pregnancy
For some families, knowing that they'll have an infant with a severe or fatal genetic condition seems too much to bear. Other families are able to adapt to the news — and to the birth — remarkably well.
Genetic counselors can share the experiences they've had with other families in your situation. But they will not suggest a particular course of action. A genetic counselor understands that what is right for one family may not be right for another.
Genetic counselors can, however, refer you to specialists for further help. For instance, many babies with Down syndrome are born with heart defects. Your counselor might encourage you to meet with a cardiologist to discuss heart surgery, and a neonatologist to discuss the care of a post-operative newborn. Genetic counselors can also refer you to social workers, support groups, or mental health professionals to help you adjust to and prepare for your complex new reality.
Finding a Genetic Counselor
Working with a genetic counselor can be reassuring and informative, especially if you or your partner have known risk factors. Talk to your doctor if you feel you would benefit from genetic counseling. Many doctors have a list of local genetic counselors they work with. You also can contact the National Society of Genetic Counselors for more information.
Reviewed by: Larissa Hirsch, MD
Date reviewed: April 06, 2017