Campomelic Dysplasia

Campomelic dysplasia is one of the more rare forms of congenital short-limb dwarfism. Its incidence is approximately 1 in 111,000 to 1 in 200,000 live births. The term "campomelic" or "camptomelic" is of Greek origin and literally means "bent limb."

 
How Campomelic Dysplasia Is Inherited

Campomelic dysplasia is typically inherited in a sporadic, autosomal dominant manner (3).

 
Causes of Campomelic Dysplasia

Campomelic dysplasia is caused by a mutation in the SOX-9 gene, localized to chromosome 17. The SOX-9 gene encodes for a transcription factor that is responsible for normal cartilage development and sexual development.

 
Physical Characteristics

Campomelic dysplasia is characterized by the bowing of the femur and tibia. Some individuals can have this condition without any appreciable bowing of the long bones but with other major features. These patients are referred to as having "acampomelic" camptomelic dysplasia. We will limit the following discussion to patients with classic campomelic dysplasia.

Campomelic dysplasia can be a lethal condition. However, a proportion of campomelic children can survive into adulthood. In the newborn period, respiratory distress may occur due to the lack of development of the cartilage rings that support the tracheobronchial tree. Although respiratory insufficiency may lead to hypoxic brain injury, in general patients with campomelic dysplasia have average intelligence.

Face & Skull:
  • Long and narrow skull
  • Prominent forehead
  • Flat face with a depressed nasal bridge
  • Micrognathism
  • Possible cleft palate
Trunk, Chest, & Spine:
  • Short neck with redundant skin at the nape of the neck
  • Small, narrow, and bell-shaped chest
  • Eleven pairs of ribs
  • Protuberant abdomen
Arms & Legs:
  • Anterior bowing of the femur and tibia.
  • A deep subcutaneous dimple over the most prominent aspect of
    the tibia.
  • Clubfeet, frequently present on both sides.
What are the X-ray characteristics?

The radiological features of campomelic dysplasia include bowing of the femur and tibia. Typically, patients exhibit delayed ossification of distal femoral and proximal tibial epiphyses. Radial heads are dislocated. Widely spaced vertical ischia and a hypoplastic pubic bone are seen in the pelvis. Vertebral pedicles are hypoplastic or nonmineralized. Cervical vertebrae are hypoplastic. The thorax is small and bell-shaped, with eleven ribs, appearing wavy and thin. The first metacarpals are short. Short middle phalanges of the second through fifth fingers are also typical (4).

 
Musculoskeletal Problems
Long Bone Bowing

Long bone bowing in campomelic dysplasia is variable. Corrective osteotomies of the femur and tibia should be performed so that the child can start standing and walking at the appropriate times. The timing of such surgery is influenced by the child’s respiratory status. Developmental milestones are delayed in campomelic dysplasia and this should be kept in mind during decision making. A period of casting is necessary in the immediate post-operative period, followed by long-term bracing to maintain correction.

Hip Dislocations

Congenital/developmental hip dislocations are typically managed along standard lines. In infancy, the mainstay of treatment is by means of a Pavlik harness. If this fails, surgery becomes necessary.

Cervical kyphosis is an initial problem, secondary to failure of formation of the anterior cervical vertebral bodies, which can lead to spinal cord compression. Thoracic kyphoscoliosis is a severe problem that may require surgery.

Clubfeet

Clubfeet should be treated along standard lines with corrective casting and surgery, depending upon the severity of the problem.

 
Problems Elsewhere in the Body
Tracheobronchial Tree

The most significant abnormality in campomelic dysplasia is the lack of development of the cartilage rings supporting the trancheobronchial tree. These cartilage rings normally keep the breathing passages open. Poor cartilage development may cause the collapse of these passages, producing extremely small airways and causing respiratory insufficiency.
At birth, the child may require a tracheostomy and long-term ventilation
at home for the first few years of life. Many do not survive past the neonatal period.

Congenital Heart Defects

Congenital heart defects were found in around 25% of cases. The most common anomaly is a patent ductus arteriosus or patent foramen ovale.
An echocardiogram should be done to evaluate for possible congenital heart disease.

Genitourinary Tract

Genitourinary Tract: Hydronephrosis (enlarged kidney), bilateral ureteral dilatation are seen in 1/3 of patients. Hypoplastic cystic kidney, renal hypoplasia, ureteral stenosis, and renal calculi have been described in the literature. These do not pose major health risks initially but require monitoring by a nephrologist/urologist in the long-term.

Sex Reversal

Some phenotypic females may genetically be males.

Hearing

Recurrent middle ear infections, poor development of bones that normally conduct sound (auditory ossicles) and abnormal skull shape are some of the factors that contribute to hearing loss. Any suspicion of hearing loss or recurrent ear infections should prompt referral to an ENT surgeon/ audiologist for further investigation.

 
What to Watch For
  • Respiratory distress in the newborn period.
  • Chromosomal analysis should be done to evaluate for possible sex reversal in phenotypic females.
  • A renal-pelvic ultrasound should be done to assess any anomalies of the genitourinary tract.
  • Cervical spine instability due to possible cervical kyphosis.
 
References
  1. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  2. Norman, EK. Pedersen, JC. Stiris, G. Van der Hagen, CB. 1993. Campomelic dysplasia-an underdiagnosed condition? European Journal of Pediatrics. 152: 331-333.
  3. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):21-24.
  4. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.

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