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Campomelic dysplasia is a rare genetic disorder. It affects the development of the skeleton, reproductive system, and face. Symptoms of campomelic dysplasia may include bowing of the legs, dislocated hips, small lungs and chest, and external genitalia that do not look clearly male or clearly female (ambiguous genitalia). In addition, infants with campomelic dysplasia have distinctive facial features including a small chin with cleft palate, prominent eyes, flat face, and a large head. Many infants die at an early age due to breathing problems. Campomelic dysplasia usually results from a new genetic change (DNA variant) in or the near the SOX9 gene. Diagnosis is based on physical findings and x-ray (radiograph) findings and may be confirmed by genetic testing. Treatment is aimed at preventing and/or managing the known symptoms and complications associated with this condition.
==Symptoms==
[[File:Autosomal dominant - en.svg|thumb|right|Diagram of autosomal dominant inheritance.]]
The following list includes the most common signs and symptoms in people with campomelic dysplasia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.
==List of signs and symptoms==
'''Campomelic dysplasia''' is a rare genetic disorder characterized by skeletal abnormalities, distinctive facial features, and, in some cases, [[sex reversal]]. It is caused by mutations in the [[SOX9]] gene, which plays a critical role in the development of the skeleton and reproductive system.
* Large head (macrocephaly)
* Short, bowed limbs
* Dislocated hips
* 11 pairs of ribs instead of 12
* Small chest and lungs
* Club feet
* Abnormally formed shoulder blades
* Distinctive facial features, including small chin, prominent eyes, and a flat face
* Cleft palate with a small lower jaw (Pierre-Robin sequence)
* External genitalia that do not look male or female (ambiguous genitalia) or normal female genitalia with a typical male chromosome pattern (46,XY)
* Weakened cartilage of the upper respiratory tract (laryngotracheomalacia)
* Many babies with campomelic dysplasia die early in infancy due to trouble breathing. People who survive may develop an abnormal curvature of the spine (scoliosis) and spine abnormalities such as anomalies of the neck bones, which compress the spinal cord, as they age. Adults with campomelic dysplasia may also have short stature and hearing loss.
Some people with features of this genetic disorder may not have bowed limbs and are said to have acampomelic campomelic dysplasia.
=== Clinical Features ===
===== 80%-99% of people have these symptoms =====
Individuals with campomelic dysplasia typically present with:
* 11 pairs of ribs
* Fibular hypoplasia
* Flat face
* Hip dislocation
* Hypoplastic inferior ilia
* Laryngomalacia
* Macrocephaly
* Micrognathia
* Narrow chest
* Low chest
* Recurrent fractures
* Respiratory insufficiency
* Scoliosis
* Short neck
* Decreased length of neck
* Small abnormally formed scapulae
* Tibial bowing
* Tracheobronchomalacia
* 30%-79% of people have these symptoms
* Ambiguous genitalia
* Femoral bowing
* Hypertelorism
* Low-set ears
* Male pseudohermaphroditism
* Proptosis
* Short stature
* Skin dimple
* Talipes equinovarus
* Club feet
===== 5%-29% of people have these symptoms =====
* '''Skeletal abnormalities''': These include [[bowing of the long bones]], particularly the [[tibia]] and [[femur]], [[hip dislocation]], and [[clubfoot]].
* Abnormality of cardiovascular system morphology
* '''Facial features''': Affected individuals often have a small [[chin]] (micrognathia), a flat face, and a prominent forehead.
* Abnormality of the sense of smell
* '''Respiratory issues''': Due to [[tracheobronchomalacia]], individuals may experience breathing difficulties.
* Depressed nasal bridge
* '''Sex reversal''': Some individuals with an [[XY karyotype]] may develop female genitalia.
* Hearing impairment
* Hydronephrosis
* Hypoplasia of olfactory tract
* Kyphosis
* Hunched back
* Ventriculomegaly
=== Cause ===
=== Genetics ===
Campomelic dysplasia is caused by genetic changes (DNA variants) or rarely, chromosome rearrangements near or in the SOX9 gene
=== Inheritance ===
Campomelic dysplasia is inherited in an [[autosomal dominant]] pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. The [[SOX9]] gene, located on chromosome 17, is crucial for [[chondrogenesis]] and [[gonadal development]]. Mutations in this gene disrupt normal development, leading to the features of campomelic dysplasia.
Campomelic dysplasia is inherited in an autosomal dominant pattern. Most cases result from new (de novo) DNA variants in or near the SOX9 gene and occur in people with no history of the genetic disorder in their family.
All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition.
=== Diagnosis ===
Each child of an individual carrying an autosomal dominant gene variant has a 50% or 1 in 2 chance of inheriting the variant and the condition. Typically, children who inherit a dominant variant will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene variant for an autosomal dominant condition and show no signs or symptoms of the condition
Diagnosis is typically based on clinical features and can be confirmed by genetic testing to identify mutations in the [[SOX9]] gene. Prenatal diagnosis is possible through [[ultrasound]] and genetic testing if there is a known family history.
==== Treatment ====
=== Management ===
There is no specific treatment for campomelic dysplasia. Treatment is aimed at preventing and/or managing the known symptoms and complications associated with this condition. For example, orthopedic care and surgery may be needed to manage an unstable spine, clubfeet, and hip abnormalities. Surgery may also be indicated for a cleft palate if present.
Specialists who may be involved in the care of someone with campomelic dysplasia include:
Management of campomelic dysplasia is supportive and symptomatic. It may include:
* Medical geneticist
* Orthopedist/Orthopedic surgeon
* Craniofacial surgeon
* Endocrinologist
* Audiologist
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* '''Orthopedic interventions''': To address skeletal abnormalities and improve mobility.
{{Medical resources
* '''Respiratory support''': For individuals with breathing difficulties.
| DiseasesDB = 33419
* '''Endocrinological evaluation''': For individuals with sex reversal or other hormonal issues.
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| OMIM = 114290
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*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=campo-dysp GeneReviews/NCBI/NIH/UW entry on Campomelic Dysplasia]
The prognosis for individuals with campomelic dysplasia varies. Many affected individuals have a shortened lifespan due to respiratory complications, but some may survive into adulthood with appropriate medical care.
Campomelic dysplasia is a rare genetic disorder characterized by skeletal abnormalities, distinctive facial features, and, in some cases, sex reversal. It is caused by mutations in the SOX9 gene, which plays a critical role in the development of the skeleton and reproductive system.
Clinical Features
Individuals with campomelic dysplasia typically present with:
Facial features: Affected individuals often have a small chin (micrognathia), a flat face, and a prominent forehead.
Respiratory issues: Due to tracheobronchomalacia, individuals may experience breathing difficulties.
Sex reversal: Some individuals with an XY karyotype may develop female genitalia.
Genetics
Campomelic dysplasia is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. The SOX9 gene, located on chromosome 17, is crucial for chondrogenesis and gonadal development. Mutations in this gene disrupt normal development, leading to the features of campomelic dysplasia.
Diagnosis
Diagnosis is typically based on clinical features and can be confirmed by genetic testing to identify mutations in the SOX9 gene. Prenatal diagnosis is possible through ultrasound and genetic testing if there is a known family history.
Management
Management of campomelic dysplasia is supportive and symptomatic. It may include:
Orthopedic interventions: To address skeletal abnormalities and improve mobility.
Respiratory support: For individuals with breathing difficulties.
Endocrinological evaluation: For individuals with sex reversal or other hormonal issues.
Prognosis
The prognosis for individuals with campomelic dysplasia varies. Many affected individuals have a shortened lifespan due to respiratory complications, but some may survive into adulthood with appropriate medical care.
