Multiple Epiphyseal Dysplasia

Epiphysis refers to the ends of long bones that are adjacent to the joints. Therefore, this disorder is one that involves more than one epiphysis. MED occurs in approximately 9 in 100,000 live births (4). Initially, two types of MED were identified: Fairbank Type (severe) and Ribbing Type (mild). However, the MED is now considered one clinically heterogenous disorder, and the two classifications have been abandoned (5).

 
How Multiple Epiphyseal Dysplasia Is Inherited

MED is typically inherited in an autosomal dominant manner (2). However, an autosomal recessive form of MED has also been idenitified (2). Due to non-allelic mutations, genetic heterogeneity does occur, resulting in a wide variability of expression.

 
Causes of Multiple Epiphyseal Dysplasia

The Fairbank type of MED is caused by a mutation in the gene encoding the cartilage oligomeric matrix protein, or COMP. A less severe form can be caused by point mutations in any three of the type IX collagen genes (COL9A1, COL9A2, COL9A3). Type IX collagen is found on the surface of type II collagen and is necessary for the integrity of articular cartilage. Another mutation in the gene that encodes matrilin-3 causes a distinctively mild form of MED. Finally, the autosomal recessive form of MED is caused by mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene or by mutations in the solute carrier family 26, member 2 gene (SLC26A2). Overall, the mutations result in a retarded formation of epiphyseal ossification centers. The bones most commonly affected are the humeral and femoral heads. Bones of the pelvis, spinal column and skull are typically normal.

 
Physical Characteristics

MED is a disorder of bone and cartilage development that results in small irregular epiphyses, proportionate short stature, frequently painful joints, and early onset degenerative arthritis. MED is not typically recognized until after two-years of age and in some cases, not until early adulthood. Typically adults will grow to be between 145 and 170 cm.

Face & Skull
  • Normal facial features
Trunk, Chest, & Spine:
  • Accentuated thoracic kyphosis
  • Possibility for blunted, flattened, or slightly ovoid vertebral bodies
Arms & Legs:
What are the X-ray characteristics?

The major radiographic features of MED include irregular epiphyses and, in childhood, irregularity of the tubular bones, usually at the hips, knees, ankles, wrists and hands. In middle to late childhood, the epiphyses are either flat or small. An important sign is the epiphyses of distal tibias are laterally malformed to produce a sloping wedge-shaped articular surface in adults. Bipartite (split) patella is common. Metaphyses are normal with mild shortening of the tubular bones. The phalanges are short and stubby, and the metacarpals have epiphyseal irregularities. Vertebral bodies are flat, with irregular end plates markedly in the thoracic spine.

 
Making the Diagnosis

Clinical features and X-rays are the mainstay of diagnosis.

Mutations in 5 known gene locations account for 50% of cases. Molecular genetic testing is available on a clinical basis for the COMP gene on chromosome 19. Prenatal diagnosis is possible for the COMP mutation, if the diagnosis is suspected on ultrasound.

Often, MED is misdiagnosed as Legg-Calvé-Perthes disease. In order to distinguish between the two conditions, bone scans and full skeletal radiographic surveys are often necessary.

 
Musculoskeletal Problems
Joints

Degenerative joint disease occurs principally in the weight-bearing joints (hips, knees, and ankles) of the lower limbs but is also seen in the shoulders. The joint deformities oftentimes cause progressive “degenerative” osteoarthroses. If gone untreated, patients may be unable to stand or walk by age 50. Around the ages of 30 to 35, joint replacement is sometimes required.

Lower Limbs

Genu varus or valgus oftentimes occur.

 
Problems Elsewhere in the Body

Apart from problems in joints, no other system is affected.

 
What to Look For

Increasing pain, decreased endurance or limping in an individual with MED may be indicative of progressive arthritis. Arthritis develops in MED due to an intrinsic abnormality in the joint cartilage as previously explained. The only solution in the longer term is a hip or shoulder joint replacement. The ankle joint may be involved in MED. Because of the early onset of degenerative arthritis, vigorous, non-weight bearing exercise must be avoided to prevent disability that would require joint replacements. Both swimming and bike riding are recommended. Generally all skeletal dysplasias warrant multidisciplinary attention.

Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

 
References
  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):17-18.
  3. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  4. Taybi, H. Lachman, RS. Skeletal Dysplasias. In "Radiology of Syndromes, Metabolic Disorders, and Skeletal Dysplasias." St. Louis: Mosby-Year Book, Inc., pp 858-870. 1996.
  5. Unger, Sheila. Hecht, Jacqueline T. Pseudoachondroplasia and Multiple Epiphyseal Dysplasia: New Etiologic Developments. American Journal of Medical Genetics, 2001; 106: 244-250.

Trusted Insights from Nemours' KidsHealth

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, diet questionnaires, and family history tracking — each helps to assess the health of you and your baby, and to predict any potential health risks.

Unlike your parents, 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:

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 simplest 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 human chromosomes carry from 25,000 to 35,000 genes. 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. 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. For example, sometimes babies have been diagnosed with spina bifida before birth. Recent research suggests that delivering a baby with spina bifida via cesarean section (avoiding the trauma of travel through the birth canal) can minimize damage to the spine — and perhaps reduce the likelihood that the child will need a wheelchair.

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 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 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, or Middle Eastern descent may carry the gene for thalassemia, a red blood cell disorder.

Meeting With a Genetic Counselor

Before you meet with a genetic counselor in person, you'll 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.

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 often will encourage you to come in for a discussion.

The counselor will study your records before meeting with you, so you can make the best use of your time together. During the session, 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.

After Counseling

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 prior to 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
  • adoption
  • 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 good 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 with whom they work. You can also contact the National Society of Genetic Counselors for more information.

Reviewed by: Louis E. Bartoshesky, MD, MPH
Date reviewed: June 2010
Originally reviewed by: Linda Nicholson, MS, MC