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Genetics Home Reference: Adams-Oliver syndrome

Posted Jan 14 2014 1:51pm
Reviewed January 2014

What is Adams-Oliver syndrome?

Adams-Oliver syndrome is a rare condition that is present at birth. The primary features are an abnormality in skin development (called aplasia cutis congenita) and malformations of the limbs. A variety of other features can occur in people with Adams-Oliver syndrome.

Most people with Adams-Oliver syndrome have aplasia cutis congenita, a condition characterized by localized areas of missing skin typically occurring on the top of the head (the skull vertex). In some cases, the bone under the skin is also underdeveloped. Individuals with this condition commonly have scarring and an absence of hair growth in the affected area.

Abnormalities of the hands and feet are also common in people with Adams-Oliver syndrome. These most often involve the fingers and toes and can include abnormal nails, fingers or toes that are fused together (syndactyly), and abnormally short or missing fingers or toes (brachydactyly or oligodactyly). In some cases, other bones in the hands, feet, or lower limbs are malformed or missing.

Some affected infants have a condition called cutis marmorata telangiectatica congenita. This disorder of the blood vessels causes a reddish or purplish net-like pattern on the skin. In addition, people with Adams-Oliver syndrome can develop high blood pressure in the vessels that carry blood from the heart to the lungs (pulmonary hypertension), which can be life-threatening. Other blood vessel problems and heart defects can occur in affected individuals.

In some cases, people with Adams-Oliver syndrome have neurological problems, such as developmental delay, learning disabilities, or abnormalities in the structure of the brain.

How common is Adams-Oliver syndrome?

Adams-Oliver syndrome is a rare disorder; its prevalence is unknown.

What genes are related to Adams-Oliver syndrome?

Mutations in the ARHGAP31, DOCK6, EOGT, or RBPJ gene can cause Adams-Oliver syndrome. Because some affected individuals do not have mutations in one of these four genes, it is likely that other genes that have not been identified are also involved in this condition. Each of the four known genes plays an important role during embryonic development, and changes in any one of them can impair this tightly controlled process, leading to the signs and symptoms of Adams-Oliver syndrome.

The proteins produced from the ARHGAP31 and DOCK6 genes are both involved in the regulation of proteins called GTPases, which transmit signals that are critical for various aspects of embryonic development. The ARHGAP31 and DOCK6 proteins appear to be especially important for GTPase regulation during development of the limbs, skull, and heart. GTPases are often called molecular switches because they can be turned on and off. The DOCK6 protein turns them on, and the ARHGAP31 protein turns them off. Mutations in the DOCK6 gene lead to production of an abnormally short DOCK6 protein that is likely unable to turn on GTPases, which reduces their activity. Mutations in the ARHGAP31 gene also decrease GTPase activity by leading to production of an abnormally active ARHGAP31 protein, which turns off GTPases when it normally should not. This decline in GTPase activity leads to the skin problems and bone malformations characteristic of Adams-Oliver syndrome.

The RBP-J protein, produced from the RBPJ gene, is an integral part of a signaling pathway known as the Notch pathway. Notch signaling controls how certain types of cells develop in the growing embryo, including those that form the bones, heart, muscles, nerves, and blood. Signaling through the Notch pathway stimulates the RBP-J protein to attach (bind) to specific regions of DNA and control the activity of genes that play a role in cellular development. The RBPJ gene mutations involved in Adams-Oliver syndrome alter the region of the RBP-J protein that normally binds DNA. The altered protein is unable to bind to DNA, preventing it from turning on particular genes. These changes in gene activity impair the proper development of the skin, bones, and other tissues, leading to the features of Adams-Oliver syndrome.

Little is known about how mutations in the EOGT gene cause Adams-Oliver syndrome. The protein produced from this gene modifies certain proteins by transferring a molecule called N-acetylglucosamine to them. It is thought that the EOGT protein modifies Notch proteins, which stimulate the Notch signaling pathway. However, the impact of the modification on Notch signaling is unclear. At least three mutations in the EOGT gene have been identified in people with Adams-Oliver syndrome, but how the genetic changes contribute to the signs and symptoms of this disorder is still unknown.

Read more about the ARHGAP31 , DOCK6 , EOGT , and RBPJ genes.

How do people inherit Adams-Oliver syndrome?

Adams-Oliver syndrome can have different inheritance patterns. When caused by mutations in the ARHGAP31 or RBPJ gene, the condition is inherited in an autosomal dominant pattern. Autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to cause the disorder.

When caused by mutations in the DOCK6 or EOGT gene, Adams-Oliver syndrome is inherited in an autosomal recessive pattern. In conditions with this pattern of inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Adams-Oliver syndrome?

These resources address the diagnosis or management of Adams-Oliver syndrome and may include treatment providers.

You might also find information on the diagnosis or management of Adams-Oliver syndrome in Educational resources and Patient support .

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing , particularly the difference between clinical tests and research tests .

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about Adams-Oliver syndrome?

You may find the following resources about Adams-Oliver syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Adams-Oliver syndrome?

  • absence defect of limbs, scalp, and skull
  • AOS
  • aplasia cutis congenita with terminal transverse limb defects
  • congenital scalp defects with distal limb reduction anomalies

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about Adams-Oliver syndrome?

Where can I find general information about genetic conditions?

What glossary definitions help with understanding Adams-Oliver syndrome?

autosomal  ; autosomal dominant  ; autosomal recessive  ; brachydactyly  ; cell  ; congenital  ; developmental delay  ; distal  ; DNA  ; embryo  ; embryonic  ; gene  ; hypertension  ; inheritance  ; molecule  ; neurological  ; oligodactyly  ; pattern of inheritance  ; prevalence  ; protein  ; pulmonary  ; recessive  ; syndactyly  ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary .

See also Understanding Medical Terminology .

References (8 links)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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