Adams-Oliver syndrome

Adams-Oliver syndrome (AOS) should be suspected when the following signs and symptoms are present:

• Aplasia cutis congenital, which may be severe and includes the skull under the area of the missing scalp, or mild and characterized by hairless patches of different size
• Terminal transverse limb defects (TTLD) spectrum, which can include small distal phalanges, short bones of the tips of the fingers or toes (distal phalanges), short and webbed fingers (brachysyndactyly), or absence of some fingers
• Heart and vascular defects

The diagnosis of Adams-Oliver syndrome is established with one of the following:

• The clinical findings of both aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD)
• Either ACC or TTLD and a first-degree relative with findings consistent with AOS
• Either ACC or TTLD and either a mutation of an AOS-related gene

In some cases, it may be possible to detect defects of the skull and/or limbs before birth (during the prenatal period) through the ultrasound.

Adams-Oliver syndrome (AOS) may be inherited in an autosomal dominant or autosomal recessive manner, depending on the gene mutation.

When AOS is caused by a mutation in the ARHGAP31 , DLL4 , NOTCH1 , or RBPJ gene, the syndrome 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 signs and symptoms of AOS. In most cases, a person inherits the mutated gene from a parent with the syndrome. In other cases, the mutation is sporadic, which means that it 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, the syndrome 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. People with AOS inherit one mutated copy of the gene from each parent. If the parent does not have AOS, then he or she is referred to as a carrier. Carriers of an autosomal recessive disease typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive disease 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.

The long-term outlook (prognosis) for people with Adams-Oliver syndrome (AOS) varies depending on the specific signs and symptoms present in each person and the degree of severity of these signs and symptoms. In some cases the prognosis is 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 a normal life expectancy. However, when people with AOS have congenital heart defects or severe problems with other organs or systems, the condition can be very severe.