Campomelic syndrome is a rare congenital disorder in which multiple anomalies are present. It is characterized by bowing and angular shape of the long bones of the legs, especially the tibia; multiple minor anomalies of the face; cleft palate; other skeletal anomalies such as abnormalities of the shoulder and pelvic area and eleven pairs of ribs instead of the usual twelve; underdevelopment of the trachea; developmental delay in some cases and incomplete development of genitalia in males such that they appear to be females.
Campomelic syndrome is a rare form of skeletal dysplasia characterized by bowing and an angular shape of the long bones of the legs. Eleven sets of ribs instead of the usual twelve may be present. The pelvis and shoulder blade may be underdeveloped. The skull may be large, long and narrow. The face may appear flat with forward tilting nostrils, high forehead, small chin, and cleft palate. Babies may regurgitate formula through the nose, are susceptible to middle ear infections and frequently experience respiratory distress.
Respiratory distress due to an underdeveloped ribcage is the most serious symptom of campomelic syndrome. The lungs may not have sufficient space to grow properly due to the underdeveloped ribcage.
Other symptoms that may occur in some patients with campomelic syndrome are dislocated hips, clubfoot, underdeveloped lungs, abnormal cervical and thoracic vertebrae,and heart and kidney abnormalities.
Some individuals with campomelic syndrome have sex reversal in which they are chromosomally male but have female genitalia and reproductive system.
Campomelic syndrome was once thought to be inherited as an autosomal recessive genetic trait but this is no longer thought to be true. Molecular genetic research has shown that a change (mutation) in a single copy of the SOX9 gene on chromosome 17 or disturbance in the regulation of this gene causes campomelic syndrome. The regulation of the SOX9 gene is sometimes disturbed by a rearrangement of genes on chromosome 17 (translocation). It is now believed that campomelic syndrome is inherited as an autosomal dominant trait. Some families have been reported in which multiple children are affected but both parents are unaffected. This may be due to one parent having a mixture of sperm or egg cells with normal and abnormal SOX9 genes (gonadal mosaicism). As a result, one or more of this parent’s children may inherit the gene mutation and exhibit the disorder even though the parent has no apparent symptoms.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Campomelic syndrome is a rare disorder that is thought to affect females twice as often as males. These numbers may not be accurate as some patients with this disorder have associated sex reversal and have been mistakenly identified as the opposite sex. Approximately one hundred cases of this disorder have been reported in the medical literature.
Diagnosis is based on clinical examination, x-rays of vertebrae, hips, chest, legs and feet, ultrasound of kidneys and echocardiogram of the heart. DNA analysis of blood can confirm a mutation in the SOX9 gene.
Treatment of respiratory problems consists of mechanical or physical breathing assistance such as positive end expiratory pressure (PEEP). Orthopedic medical care including surgery may help alleviate some of the more serious bone deformities. The bowed tibiae usually straighten spontaneously.
It may be appropriate to reassign the sex of a male with female genitalia to be female.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
The Vertical Expandable Prosthetic Titanium Rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. The titanium rib was developed at the University of Texas Health Science Center in San Antonio. It is manufactured by Synthes Spine Co.. http://www.synthes.com/sites/NA/Products/Spine/Screw_Hook_Rod_and_Clamp_System/Pages/VEPTR_and_VEPTR_II.aspx
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Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 114290: Last Edit Date: 10/17/02.