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Adams-Oliver syndrome (AOS) is a rare inherited condition present at birth that involves changes to the limbs and scalp. Symptoms may include areas of missing skin on the scalp, limb abnormalities, heart defects, neurological concerns, and issues with the eyes. AOS is caused by harmful changes (mutations) in the ARHGAP31, DLL4, DOCK6, EOGT, NOTCH1, or RBPJ genes. Some people with AOS do not have a mutation in one of these genes AOS has different inheritance patterns based on the gene involved. Mutations in these genes can follow either an autosomal dominant or recessive inheritance pattern. There is no cure for AOC. However, it can be managed by monitoring for and treating the symptoms. This is typically done by several different healthcare providers such as pediatricians, cardiologists, and plastic surgeons.
Adams–Oliver syndrome (AOS) is a rare congenital disorder characterized by aplasia cutis congenital and terminal transverse limb defects and defects of the scalp and cranium (cutis aplasia congenital), transverse defects of the limbs, and mottling of the skin.
Causes
AOS is known to be caused by harmful changes (mutations) in several genes: ARHGAP31, DLL4, DOCK6, EOGT, NOTCH1, or RBPJ. Symptoms vary based on which gene is involved. In about 50% of patients, no mutations in these genes are found.
Most cases follow an autosomal dominant inheritance pattern through mutations in the ARHGAP31, DLL4, NOTCH1, and/or RBPJ genes. The ARHGAP31, DLL4, and NOTCH1 genes have shown incomplete penetrance. This means that people who carry mutations in these genes may not display symptoms of AOS. For the RBPJ gene, incomplete penetrance has not been shown. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular genetic condition. The non-working gene can be inherited from either parent or can be the result of a new harmful gene change (de novo mutation) in the affected individual that was not inherited from the parents. The chance of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
AOS that involves the EOGT or DOCK6 genes follows an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier of the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working 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 working genes from both parents is 25%. The risk is the same for males and females.
Some researchers suspect that the physical features associated with AOS may result from interrupted blood flow through certain arteries during fetal development. These features are seen in a group of developmental conditions called “subclavian artery supply disruption sequence (SASDS).” Other conditions in this group include Poland syndrome, Klippel-Feil syndrome, Moebius syndrome, and Sprengel deformity.
Diagnosis
The diagnosis of Adams-Oliver syndrome can be made when an infant has both the absence of skin on the scalp and changes in the fingers, hands, toes, and/or feet. Also, a diagnosis can be made if an individual both has aplasia cutis congenital or changes of the fingers, hands, toes, and/or feet, and has a first-degree relative with AOS. Lastly, a diagnosis can be made when an individual has either of these two main features: the absence of skin or malformation of the fingers, hands, toes, and/or feet, and a single mutation in the autosomal dominant related gene (ARHGAP31, DLL4, NOTCH1, or RBPJ) or two mutations in an autosomal recessive related gene (DOCK6 or EOGT).
Treatment
The treatment of Adams-Oliver syndrome is directed towards the specific symptoms that are apparent in an individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedic and plastic surgeons, cardiologists, ophthalmologists, physical therapists, and other health care professionals may be needed for an individual’s treatment and surveillance of skin, limb, cardiovascular, neurological, and eye concerns.
In many patients, scalp defects may heal without treatment within the first few months of life. Skin grafting, skull surgery, and/or other surgical procedures may be required for individuals with AOS who have skull problems. Wearing helmets may be recommended for some children with AOS to prevent trauma to the head and potential damage to the wide blood vessels.
Physical therapy, surgery, and/or the use of artificial limbs may be recommended for children who have a partial or complete absence of fingers, toes, hands, feet, and/or lower legs.
A complete medical evaluation should be done to look for potential concerns with the heart. Cardiovascular issues such as structural heart problems may require surgery.
Monitoring for symptoms every year is recommended for infants with AOS. Echocardiographs should be done every year until the age of three for signs of pulmonary hypertension. For neurological concerns, affected children should have a neurological exam and assessment of psychomotor development every year. For eye concerns, affected children should see a pediatric ophthalmologist up until the age of three to look for any problems with the eyes.
Genetic counseling is recommended for individuals with AOS and their families. Other treatments for this disorder are symptomatic and supportive.
References
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