Adams–Oliver syndrome

Overview

Adams–Oliver syndrome (AOS) is a rare congenital disorder primarily characterized by defects of the scalp and skull, as well as limb abnormalities. It may also involve abnormalities in blood vessels, the heart, and the central nervous system. AOS was first described in 1945 and has since been recognized as a condition with significant variability in its presentation and severity. It can affect individuals from birth and requires a multidisciplinary approach to care.

Causes

Adams–Oliver syndrome is caused by mutations in several genes, most commonly:

• ARHGAP31

• DOCK6

• NOTCH1

• RBPJ

• EOGT

These genes are involved in blood vessel development, cell signaling, and tissue formation during embryogenesis. AOS can follow different inheritance patterns:

• Autosomal dominant (most common, often due to NOTCH1 or ARHGAP31 mutations)

• Autosomal recessive (associated with DOCK6 or EOGT mutations)

Symptoms

Symptoms and severity of Adams–Oliver syndrome can vary widely between individuals. Common features include:

1. Scalp and Skull Abnormalities:

• Aplasia cutis congenita: Localized absence of skin on the scalp, often with underlying skull bone defects

2. Limb Defects:

• Shortened or missing fingers or toes (brachydactyly, oligodactyly)

• Abnormal nails or toenails

• Webbing (syndactyly) or clubfoot

3. Vascular Malformations:

• Cutis marmorata telangiectatica congenita (CMTC): Marbled skin with dilated blood vessels

• Prominent veins or vascular anomalies

4. Cardiac and Neurological Involvement (in some cases):

• Congenital heart defects (e.g., ventricular septal defects)

• Seizures, developmental delays, or intellectual disability

Diagnosis

Diagnosis of AOS is based on clinical features, family history, and genetic testing. Key diagnostic steps include:

• Physical examination: To identify scalp, limb, and skin anomalies

• Imaging studies: Skull X-ray, MRI, or CT to assess bone and brain structure

• Echocardiogram: To evaluate for congenital heart defects

• Genetic testing: To identify mutations in known AOS-associated genes

Diagnosis can be confirmed even without genetic testing if hallmark features are present.

Treatment

There is no cure for Adams–Oliver syndrome, so treatment focuses on symptom management and supportive care. A multidisciplinary team typically includes dermatologists, orthopedic surgeons, cardiologists, neurologists, and geneticists. Treatment options include:

• Surgical repair: For scalp or skull defects to protect underlying tissues

• Limb reconstruction: Prosthetics or orthopedic interventions for functional improvement

• Cardiac surgery or medications: For heart defects

• Developmental therapies: Physical, occupational, and speech therapy if developmental delays are present

• Skin care: For vascular abnormalities or wound management

Prognosis

The prognosis for individuals with Adams–Oliver syndrome depends on the severity of their symptoms. Many people with mild scalp and limb defects lead normal lives with minimal intervention. However, those with serious cardiac or neurological involvement may face more complex challenges and require long-term care.

With early intervention and comprehensive medical support, many affected individuals can achieve good functional outcomes and an improved quality of life.