Adams–Oliver syndrome

Adams–Oliver syndrome
Classification and external resources
Specialty
OMIM	100300
DiseasesDB	32741
Patient UK	Adams–Oliver syndrome

Adams–Oliver syndrome (AOS) is a rare congenital disorder characterized by defects of the scalp and cranium (cutis aplasia congenita), transverse defects of the limbs, and mottling of the skin.

Characteristics

Two key features of AOS are aplasia cutis congenita with or without underlying bony defects and terminal transverse limb defects. Cutis aplasia congenita is defined as missing skin over any area of the body at birth; in AOS skin aplasia occurs at the vertex of the skull. The size of the lesion is variable and may range from solitary round hairless patches to complete exposure of the cranial contents. There are also varying degrees of terminal limb defects (for example, shortened digits) of the upper extremities, lower extremities, or both. Individuals with AOS may have mild growth deficiency, with height in the low-normal percentiles. The skin is frequently observed to have a mottled appearance (cutis marmorata telangiectata congenita). Other congenital anomalies, including cardiovascular malformations, cleft lip and/or palate, abnormal renal system, and neurologic disorders manifesting as seizure disorders and developmental delay are sometimes observed. Variable defects in blood vessels have been described, including hypoplastic aortic arch, middle cerebral artery, pulmonary arteries. Other vascular abnormalities described in AOS include absent portal vein, portal sclerosis, arteriovenous malformations, abnormal umbilical veins, and dilated renal veins.

Genetics

AOS was initially described as having autosomal dominant inheritance due to the reports of families with multiple affected family members in more than one generation. The severity of the condition can vary between family members, suggestive of variable expressivity and reduced penetrance of the disease-causing allele. Subsequently, it was reported that some cases of AOS appear to have autosomal recessive inheritance, perhaps with somewhat more severe phenotypic effects. Three AOS genes have been identified, ARHGAP31, DOCK6, and RBPJ. The first two genes listed regulate proteins CDC421 and RAC1.

Another gene that has been associated with this condition is Notch1.

Mechanism

The precise mechanism underlying the congenital abnormalities observed in AOS is unknown. Similar terminal transverse limb anomalies and cardiovascular malformations are seen in animal models of hypoxic insults during the first trimester. Combined with the common association of cardiac and vascular abnormalities in AOS, it has been hypothesized that the spectrum of defects observed in AOS could be due to a disorder of vasculogenesis.

So far, the disease-causing genetic defect in AOS has not been definitively identified. In rare cases, AOS can be associated with chromosomal translocations. A panel of candidate genes (including ALX4, ALX1, MSX1, MSX2, P63, RUNX2 and HOXD13) have been tested but no disease-causing mutations have been identified.

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	Minor features
Terminal transverse limb defects	Cutis marmorata
Aplasia cutis congenita	Congenital heart defect
Family history of AOS	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.

Management

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.

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.

Epidemiology

AOS is a rare genetic disorder and the annual incidence or overall prevalence of AOS is unknown. Approximately 100 individuals with this disorder have been reported in the medical literature.

History

AOS was first reported in a family with eight affected members.