Adams Oliver syndrome

Synonyms

5

Overview

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 blood vessels between the heart and 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.

Symptoms

The syndrome is characterised by congenital scalp and skull defects. These defects can range from mild, with some skin and hair defect, through to severe when there may be defects of the underlying bone. Rarely, bleeding occurs from dilated veins that are sometimes associated with severe scalp defects. Other features that may occur include eye anomalies, accessory nipples cutis marmorata telangiectatica congenita, haemangiomas, skin tags and woolly hair. Intellectual development is generally within normal limits, even in individuals with large cranial bone defects, although learning disabilities have been reported.

Causes

Adams-Oliver syndrome is a rare disorder; its prevalence is unknown. It may be inherited in an autosomal dominant or autosomal recessive manner, depending on the genetic cause.

When AOS is caused by a mutation in the ARHGAP31, DLL4, NOTCH1, or RBPJ gene, it is inherited in an autosomal dominant manner. This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause features of AOS. In most cases, a person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of AOS. When a person with an autosomal dominant form of AOS has children, each child has a 50% (1 in 2) chance to inherit the disease-causing mutation.

When AOS is caused by mutations in the DOCK6 or EOGT gene, it is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) chance to be affected, a 50% (1 in 2) chance to be an unaffected carrier like each parent, and a 25% chance to be unaffected and not be a carrier.

Diagnosis

The diagnosis of AOS is a clinical diagnosis based on the specific features described above. A system of major and minor criteria was proposed.

Major features:

  • Terminal transverse limb defects 
  • Aplasia cutis congenita 
  • Family history of AOS

Minor features:

  • Cutis marmorata
  • Congenital heart defect
  • Vascular anomaly

The combination of two major criteria would be sufficient for the diagnosis of AOS, while a combination of one major and one minor feature would be suggestive of AOS. There is currently no genetic testing that can be performed in order to confirm or rule out this condition.

Prognosis

The overall prognosis is excellent in most cases. Most children with Adams Oliver Syndrome can likely expect to have a normal life span. However, individuals with more severe scalp and cranial defects may experience complications such as hemorrhage and meningitis, leading to long-term disability.

The long-term outlook (prognosis) for people with Adams-Oliver syndrome varies depending on the specific features present and the severity in each person. In some cases the prognosis is reportedly excellent, although surgery often is needed to close the skull or scalp defects that may expose the brain. It seems likely that mild forms (for example, those with only skin and/or skeletal abnormalities) are associated with a better prognosis and possibly a normal life expectancy. However, a proportion of affected people have congenital heart defects or severe problems with other organs or systems, which can carry a risk of disability or death. The presence and/or severity of internal abnormalities likely determine the prognosis in each person.

Treatment

Although bald ulcerated areas of the skull usually heal on their own, occasionally plastic surgery is needed. While surgery may be indicated for some of the skull defects, treatment is otherwise symptomatic. Management focuses on ameliorating the effects of any skull or limb defects. Also, Management of AOS is largely symptomatic and aimed at treating the various congenital anomalies present in the individual. When the scalp and/or cranial bone defects are severe, early surgical intervention with grafting is indicated.

Resources

  • Genetics Home Reference
  • NIH