martes, 11 de abril de 2017

Campomelic dysplasia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program

Campomelic dysplasia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program

National Center for Advancing and Translational SciencesGenetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Campomelic dysplasia

Campomelic dysplasia is a genetic disorder that affects the development of the skeleton and reproductive system. This condition is often life-threatening in the newborn period because of respiratory problems. Affected children are typically born with bowing of the long bones in the legs and may also have bowing in the arms. About 75% of the children have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Common findings include distinctive facial features (including a small chin, prominent eyes, flat face, and a large head compared to their body size); a particular group of physical features, called Pierre-Robin sequence; short legs; dislocated hips; underdeveloped shoulder blades; bone abnormalities in the neck; and feet that are abnormally rotated (club feet). 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 person with the genetic disorder.[1] Treatment typically includes multiple surgeries to correct some of the abnormalities present.[2] 

Bowing of the limbs, the feature that gave the disorder its name (campomelic is derived from the Greek for “bent limb), does not have to be present. When the limbs are not bowed, the term “acampomelic campomelic dysplasia” is used.[1]
Last updated: 4/4/2017

The signs and symptoms may include:[1][2]
  • Large head compared to the body size
  • Congenital (present at birth) short and bowed long bones of the legs, and occasionally of the arms and skin dimples caused by the bowed bents, especially on the lower legs (pretibial skin dimples)
  • Dislocated hips
  • Underdeveloped shoulder blades
  • 11 pairs of ribs instead of 12
  • Feet that are abnormally rotated (club feet)
  • Distinctive facial features, including small chin, prominent eyes, and a flat face
  • Pierre-Robin sequence, which 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)
  • External genitalia that do not look clearly male or clearly female (ambiguous genitalia) or normal female genitalia with a typical male chromosome pattern (46,XY) in about 75% of the cases. Internal reproductive organs may not correspond with the external genitalia. People with campomelic dysplasia can have testes, ovaries, or a combination of the two
  •  Weakened cartilage of the upper respiratory tract (laryngotracheomalacia) partially blocking the airway and causing severe difficulty breathing which may lead to poor survival of infants with campomelic dysplasia
People who survive childhood may develop an abnormal curvature of the spine (scoliosis) and other spine abnormalities such as anomalies of the neck bones, which compress the spinal cord, as they age. People with campomelic dysplasia may also have short stature and hearing loss.[1]

Some people with features of this genetic disorder may not have bowed limbs and are said to have acampomelic campomelic dysplasia.[2] 

Last updated: 4/4/2017
The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.
Signs and SymptomsApproximate number of patients (when available)Help
11 pairs of ribsVery frequent 
(present in 80%-99% of cases)
Cleft palateVery frequent 
(present in 80%-99% of cases)
Fibular hypoplasiaVery frequent 
(present in 80%-99% of cases)
Flat faceVery frequent 
(present in 80%-99% of cases)
Hip dislocationVery frequent 
(present in 80%-99% of cases)
Hypoplastic inferior iliaVery frequent 
(present in 80%-99% of cases)
LaryngomalaciaVery frequent 
(present in 80%-99% of cases)
MacrocephalyVery frequent 
(present in 80%-99% of cases)
MicrognathiaVery frequent 
(present in 80%-99% of cases)
Narrow chestVery frequent 
(present in 80%-99% of cases)
Last updated: 3/10/2017

Campomelic dysplasia is inherited in an autosomal dominant pattern, which means that one copy of the altered (mutated) gene in each cell is enough to cause the disorder. If a person has an autosomal dominant genetic disorder, with each pregnancy, there is a 50% (1 in 2) chance for the embryo to have the genetic disorder, and a 50% chance for the embryo to not have the genetic disorder. 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 genetic disorder.

Most cases of campomelic dysplasia result from new (de novomutations in or near the SOX9 gene and occur in people with no history of the genetic disorder in their family. Rarely, people with campomelic dysplasia inherit a chromosome abnormality (such as a deletionde 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 people with campomelic dysplasia have the disorder as the result of a de novo mutation, parents of these people usually do not have signs and symptoms of the genetic disorder. 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 a person has two or more cell lines with different genetic or chromosomal make-ups. A person 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 genetic disorder. If some egg or sperm cells carry the mutation or chromosome abnormality, the genetic disorder can be inherited by that person's children. Familial translocations (when a whole chromosome or segment of a chromosome becomes attached to or interchanged with another whole chromosome or segment) involving the SOX9 gene have been reported but are rare.

The risk to siblings of a person with campomelic dysplasia depends on the genetic status of the affected person'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 a person with the genetic disorder are at an estimated 2%-5% risk, even if the disease-causing mutation found in the person with campomelic disorder 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]

Because of the complexity of the inheritance of campomelic dysplasia, we recommend speaking with a genetics professional. 
Last updated: 4/4/2017

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

    Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

    Patient Registry

    Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

      Genetics Resources

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Campomelic dysplasia. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Campomelic dysplasia. Click on the link to view a sample search on this topic.

            Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question
            • I carry a mutation in the SOX9 gene but I do not have any signs or symptoms of campomelic dysplasia. I have had several pregnancies; one resulted in a child with the condition who later passed away, two resulted in pregnancy termination because the fetuses were found to have the condition, and 2 resulted in miscarriages. I was told that the risk for each of my pregnancies to be affected with this condition was 50%. If this is the case, why does it seem like all of my pregnancies have been affected? See answer

            1. Campomelic dysplasia. Genetics Home Reference. 2014;
            2. Unger S, Scherer G & Superti-Furga A. Campomelic dysplasia. GeneReviews. May 9, 2013;

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