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Genetic and Rare Diseases Information Center (GARD)

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Campomelic dysplasia


Other Names for this Disease

  • CMD1
  • CMPD
  • CMPD1
  • CMPD1/SRA1
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Overview

What is campomelic dysplasia?

What are the signs and symptoms of campomelic dysplasia?

How is campomelic dysplasia inherited?

What is campomelic dysplasia?

Campomelic dysplasia is a severe disorder that affects the development of the skeleton and reproductive system. This condition is often life-threatening in the newborn period. Affected individuals are typically born with bowing of the long bones in the legs and may also have bowing in the arms; short legs; dislocated hips; underdeveloped shoulder blades; bone abnormalities in the neck; feet that are abnormally rotated (club feet); external genitalia that do not look clearly male or clearly female (ambiguous genitalia); distinctive facial features (including a small chin, prominent eyes, flat face, a large head compared to their body size); a particular group of physical features, called Pierre-Robin sequence; and other abnormalities. It is caused by mutations in the SOX9 gene and is inherited in an autosomal dominant pattern, although most cases result from a new mutation in the affected individual.[1] Treatment typically includes multiple surgeries to correct some of the above-mentioned abnormalities.[2] When affected individuals have features of this disorder but do not have bowed limbs, they are said to have acampomelic campomelic dysplasia.[1]
Last updated: 12/29/2010

What are the signs and symptoms of campomelic dysplasia?

Individuals with campomelic dysplasia are typically born with bowing of the long bones in the legs, and they are occasionally born with bowing in the arms. Bowing can cause characteristic skin dimples to form over the curved bone, especially on the lower legs. People with campomelic dysplasia also usually have short legs, dislocated hips, underdeveloped shoulder blades, 11 pairs of ribs instead of 12, bone abnormalities in the neck, and feet that are abnormally rotated (club feet). When affected individuals have features of this disorder but do not have bowed limbs, they are said to have acampomelic campomelic dysplasia. Many people with campomelic dysplasia have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Approximately 75 percent of affected individuals with a typical male chromosome pattern (46,XY) have ambiguous genitalia or normal female genitalia. Internal reproductive organs may not correspond with the external genitalia; they can be male (testes), female (ovaries), or a combination of the two. Affected individuals have distinctive facial features, including a small chin, prominent eyes, and a flat face. They also have a large head compared to their body size. A particular group of physical features, called Pierre-Robin sequence, is common in people with campomelic dysplasia. Pierre-Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). People with campomelic dysplasia are often born with weakened cartilage that forms the upper respiratory tract. This abnormality, called laryngotracheomalacia, partially blocks the airway and causes difficulty breathing. Laryngotracheomalacia contributes to the poor survival of infants with campomelic dysplasia. Only a few people with campomelic dysplasia survive past infancy. As these individuals age, they may develop an abnormal curvature of the spine (scoliosis) and other spine abnormalities that compress the spinal cord. People with campomelic dysplasia may also have short stature and hearing loss.[1]
Last updated: 12/29/2010

How is campomelic dysplasia inherited?

Campomelic dysplasia is inherited in an autosomal dominant pattern, which means that one copy of the altered (mutated) gene in each cell is sufficient to cause the disorder. If an individual has an autosomal dominant condition, with each pregnancy there is a 50% (1 in 2) chance for the embryo to have the condition, and a 50% chance for the embryo to not have the condition. It should be noted that this risk is for each separate pregnancy; it does not mean that 50% of an individual's pregnancies will be affected by the condition.

Most cases of campomelic dysplasia result from new (de novo) mutations in or near the SOX9 gene and occur in people with no history of the disorder in their family. Rarely, affected individuals inherit a chromosome abnormality (such as a deletion, de novo translocation, or inversion) near or involving the SOX9 gene from a parent who may or may not show mild signs and symptoms of campomelic dysplasia.[1][2]

Because most individuals with campomelic dysplasia have the disorder as the result of a de novo mutation, parents of these individuals are not typically affected. However, a few adults have been diagnosed with campomelic dysplasia after the birth of an affected child or the diagnosis of a fetus during pregnancy.

Recurrence in siblings has occurred, and mosaicism has been reported. Mosaicism is when an individual has two or more cell lines with different genetic or chromosomal make-ups. An individual may have some cells with the mutation and some cells without (including egg or sperm cells) and not have any signs or symptoms of the condition. If some egg or sperm cells carry the mutation or chromosome abnormality, the condition can be inherited by that individual's offspring. Familial translocations (when a whole chromosome or segment of a chromosome becomes attached to or interchanged with another whole chromosome or segment) invloving the SOX9 gene have been reported, but are rare.

The risk to siblings of an affected individual depends on the genetic status of the affected individual's parents. If a non-mosaic parent of the affected individual has signs and symptoms of the condition, the risk to the siblings is 50%. Because parental mosaicism has been reported, the siblings of an affected individual are at an estimated 2%-5% risk, even if the disease-causing mutation found in the affected individual cannot be detected in either parent. 

The risk to a child of a parent with a non-mosaic SOX9 gene mutation is 50% (1 in 2). If the parent has a chromosome rearrangement involving SOX9, the risk would depend on the specific chromosome abnormality.[2]
Last updated: 12/29/2010

References
  1. Campomelic dysplasia. Genetics Home Reference. May 2009; http://ghr.nlm.nih.gov/condition/campomelic-dysplasia. Accessed 12/29/2010.
  2. Sheila Unger, Gerd Scherer, Andrea Superti-Furga. Campomelic dysplasia. GeneReviews. July 31, 2008; http://www.ncbi.nlm.nih.gov/books/NBK1760/#campo-dysp.Management. Accessed 12/29/2010.


Other Names for this Disease
  • CMD1
  • CMPD
  • CMPD1
  • CMPD1/SRA1
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.