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."
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.
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
- 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:
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).
Long Bone Bowing
Long bone bowing in campomelic dysplasia is variable. Corrective osteotomies of the femur and tibia should be preformed 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.
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 should be treated along standard lines with corrective casting and surgery, depending upon the severity of the problem.
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.
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.
Some phenotypic females may genetically be males.
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.
- Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
- Norman, EK. Pedersen, JC. Stiris, G. Van der Hagen, CB. 1993. Campomelic dysplasia-an underdiagnosed condition? European Journal of Pediatrics. 152: 331-333.
- Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):21-24.
- Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
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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 subunits called nucleotides. Each nucleotide contains a phosphate molecule, a sugar molecule (deoxyribose), and one of four coding molecules called bases (adenine, guanine, cytosine, or thymine). The sequence of these four bases determines the genetic code.
The specific segments of DNA that contain the instructions for making specific body proteins are called genes. Right now, scientists believe that human DNA carries from 25,000 to 35,000 genes. Some genes direct the formation of proteins that eventually determine physical features such as brown eyes or curly hair. Others provide instructions for the body to produce important chemicals called enzymes (which help control the chemical reactions in the body).
Sometimes, depending on the codes of a specific gene, even a small error within the DNA structure can mean serious problems for the entire body. Sometimes, an error in just one gene can result in a life that's shortened or physically difficult.
Genes are found in specific segments along the length of human DNA, 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, 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.
Abnormal Numbers of Chromosomes (Trisomies and Monosomies)
Genetic problems can happen for many reasons. Sometimes, a mistake occurs during cell division, causing an error in the chromosome number either before or shortly after conception. The developing embryo then grows from cells that have either too many chromosomes or too few.
In trisomy, for example, there are three copies of one particular chromosome instead of the normal two (one from each parent). Down syndrome, trisomy 18 (Edwards) syndrome, and trisomy 13 (Patau) syndrome are examples of this type of genetic problem.
Trisomy 18 syndrome affects 1 out of every 3,000 newborns. Children with this syndrome have a low birth weight and a small head, mouth, and jaw. Their hands typically form closed fists with abnormal finger positioning. They also might have malformations involving the hips and feet, heart and kidney problems, and intellectual disability (also called mental retardation). Only about 5% of these children live longer than 1 year.
Trisomy 13 syndrome affects 1 out of every 5,000 newborns. This syndrome causes cleft lip, flexed fingers with extra digits, hemangiomas (blood vessel malformations) of the face and neck, and many different structural abnormalities of the skull and face. It can also cause malformations of the ribs, heart, abdominal organs, and sex organs. Long-term survival is unlikely but possible.
In monosomy, another form of number error, one member of a chromosome pair is missing. There are too few chromosomes rather than too many.
Deletions, Translocations, and Inversions
Sometimes it's not the number of chromosomes that's the problem, but that chromosomes are incomplete or abnormally shaped. In both deletions and microdeletions, for example, some small part of a chromosome is missing. In a microdeletion, the missing part of a chromosome is usually so small that it amounts to a single gene or only a few genes.
Important 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 1 out of every 500 newborns), bits of chromosomes shift from one chromosome to another. Most translocations are "balanced," which means there is no net gain or loss of genetic material; some are "unbalanced," which means some genetic material is extra or missing.With inversions (which affect about 1 out of every 100 newborns), small parts of the DNA code seem to be snipped out and reinserted flipped over. Translocations may be either inherited from a parent or arise 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, adults 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.
Genetic Problems (cont.)
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. Turner syndrome is the name of the disorder affecting girls born with only one X chromosome, whereas boys with Klinefelter syndrome are born with XXY or XXXY.
Sometimes, too, a genetic problem is X-linked, meaning that it's associated with change in a gene carried by the X chromosome. Fragile X syndrome, which causes intellectual disability in boys, is one such disorder. Other diseases that are carried by genes 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 on the affected X will be reduced. Males, on the other hand, only have one X chromosome and are almost always the ones who have the substantial effects of the X-linked disorder.
Some genetic problems are caused by a single gene that's 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 entirely normal. To pinpoint the defective gene, scientists use sophisticated DNA screening techniques. Some examples of genetic illnesses caused by a single problem gene include: phenylketonuria (PKU), cystic fibrosis, sickle cell anemia, Tay-Sachs disease, and achondroplasia (a type of dwarfism).
Although experts originally believed that no more than 3% of all human diseases were caused by errors in a single gene, new research suggests that this may be 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 several different types of cancer.
Oncogenes (Cancer-Causing Genes)
Researchers have identified 20 to 30 cancer-susceptibility genes that greatly increase a person's odds of getting some form of malignancy. For example, a gene on chromosome number 9 may be linked to basal cell carcinoma, a common skin cancer. This gene, labeled PTC or patched, someday might be important in screening for this type of cancer. Another gene (HNPCC) that is carried by 1 out of every 300 Americans might greatly increase someone's risk for colon cancer. And the doubly dangerous gene BRCA-1 seems to give women an 85% chance of developing breast cancer as well as a 50% chance of ovarian tumors.
Other Genetically Linked Diseases
Altered genes may play a role in the development of many other devastating illnesses. Parkinson's disease, for example, may be linked to a gene on chromosome number 4, and multiple sclerosis may be linked to alterations in a gene on chromosome number 6. Alzheimer's disease, linked to a gene on chromosome 19, can already be diagnosed (in some cases) by screening for that altered gene, although such screening is viewed by many as controversial.
Although heart disease and diabetes appear to be related to simultaneous changes in many different genes, the first of these may already have been identified. According to the American Heart Association, this gene may be an artery-clogging gene that almost doubles the risk of fatty deposits blocking the coronary arteries. Having the gene may also triple someone's chances of getting adult-onset diabetes.
It's important to note that much of the newest information from genetic research has not yet been translated into useful screening tests. However, experts predict that this will soon change, and they estimate that the number of available genetic tests will increase dramatically in the years to come.