Adam-Oliver syndrome (AOS) is a rare congenital disorder apparent at birth. The condition primarily affects the development of the scalp and limbs, though its impact can extend to the cardiovascular and central nervous systems. Its presentation varies significantly among individuals, with an estimated incidence of approximately 1 in 225,000 live births.
Core Physical Characteristics
A primary feature of Adam-Oliver syndrome is a scalp defect known as aplasia cutis congenita (ACC). This condition is characterized by the absence of a localized patch of skin, often on the top of the head (the vertex). The severity of ACC ranges from a small, superficial ulcer to a larger lesion that may expose the underlying skull bone. The affected area often heals but leaves a permanent, hairless scar.
Limb abnormalities, known as terminal transverse limb defects, are another characteristic of AOS. These malformations affect the outermost parts of the limbs, such as the fingers and toes. Defects can include short digits (brachydactyly), missing digits (oligodactyly), or fused digits (syndactyly). Nail development can also be affected, with nails appearing small or entirely absent on the affected digits, and the anomalies are often asymmetrical.
A third characteristic sometimes seen is cutis marmorata telangiectatica congenita (CMTC). This skin condition is caused by abnormalities in small blood vessels, resulting in a persistent, net-like pattern of red or purple discoloration. While not present in all individuals with AOS, its appearance alongside scalp and limb defects is highly indicative of the syndrome.
Associated Health Complications
Some individuals with Adam-Oliver syndrome experience complications involving other organ systems. Cardiovascular malformations can include structural heart defects, such as a ventricular septal defect or Tetralogy of Fallot. Blood vessel problems can also arise, including pulmonary hypertension, a form of high blood pressure in the lungs that can be life-threatening.
Neurological issues may also be present. These can range from structural brain abnormalities, like an underdeveloped corpus callosum or hydrocephalus, to functional challenges such as developmental delays or seizures. While the extent of these problems is variable, many people with AOS have normal cognitive development.
Ocular, or eye, abnormalities have also been reported. These can include conditions like microphthalmia, where one or both eyes are abnormally small, or strabismus, where the eyes do not align properly. However, many individuals with AOS only exhibit the core scalp and limb characteristics without these additional complications.
Genetic Origins and Inheritance
Adam-Oliver syndrome is caused by mutations in genes involved in embryonic development. To date, mutations in at least six distinct genes have been identified as causes of AOS:
- ARHGAP31
- DOCK6
- EOGT
- NOTCH1
- DLL4
- RBPJ
These genes are involved in cellular processes that regulate the development of blood vessels, the skeleton, and other tissues. For instance, the NOTCH1, DLL4, and RBPJ genes are part of the Notch signaling pathway, which helps guide the formation of the heart and blood vessels.
The condition is passed down in two main patterns. The most common is autosomal dominant inheritance, where a mutation in one copy of a responsible gene is enough to cause the disorder. In this pattern, an affected parent has a 50% chance of passing the condition to each child, which explains why it can appear in multiple generations.
A less common pattern is autosomal recessive inheritance, where an individual must inherit two mutated copies of a gene, one from each parent. Parents who carry one mutated copy are known as carriers and typically do not show symptoms. AOS can also result from a new (de novo) mutation, where the genetic change occurs for the first time in a child with no family history of the disorder.
Diagnosis and Management
The initial diagnosis of Adam-Oliver syndrome is based on a clinical evaluation after birth. A physician identifies the characteristic combination of aplasia cutis congenita on the scalp and terminal transverse limb defects, which is often sufficient for a diagnosis. To confirm the findings and assess the condition’s extent, doctors may use imaging studies like X-rays or an MRI to check for underlying abnormalities.
Genetic testing provides a definitive diagnosis by identifying a mutation in a known causative gene. This confirmation helps with understanding the specific type of AOS and is used for genetic counseling. Counseling informs families about inheritance patterns and the likelihood of the condition in future pregnancies. Antenatal diagnosis via ultrasound is sometimes possible if defects are visible before birth.
There is no cure for AOS, so management is tailored to an individual’s symptoms and requires a multidisciplinary team of specialists. This team may include dermatologists for wound care of the scalp, orthopedic surgeons to address limb differences, and cardiologists to monitor for heart conditions. Treatment strategies can include specialized dressings or surgery for scalp defects, physical therapy, prosthetics to aid mobility, and monitoring for associated health complications.