Apert syndrome

Overview

Apert Syndrome is a rare genetic disorder characterized by the premature fusion of certain skull bones, a condition known as craniosynostosis. This early fusion affects the shape of the head and face. In addition, people with Apert syndrome often have syndactyly (webbing or fusion of fingers and toes), facial abnormalities, and varying degrees of developmental delay. It is one of the craniosynostosis syndromes and falls under a group of conditions known as acrocephalosyndactyly disorders.

The condition is congenital, meaning it is present at birth, and affects approximately 1 in 65,000 to 88,000 newborns worldwide.

Causes

Apert syndrome is caused by mutations in the FGFR2 gene (fibroblast growth factor receptor 2). This gene plays a crucial role in the development and maintenance of bone and other tissues. The mutation leads to abnormal signaling that causes bones to fuse prematurely.

The condition is inherited in an autosomal dominant manner, meaning only one copy of the altered gene is sufficient to cause the disorder. However, most cases occur due to new (de novo) mutations, often associated with increased paternal age.

Symptoms

Symptoms and physical characteristics of Apert syndrome vary, but they commonly include:

Craniofacial Abnormalities:

• Premature fusion of skull bones (craniosynostosis), often causing a tall, narrow skull (acrocephaly)

• Flat or sunken midface (midface hypoplasia)

• Wide-set, bulging eyes (proptosis)

• Beaked nose

• Underdeveloped upper jaw (maxillary hypoplasia)

Hand and Foot Abnormalities:

• Syndactyly of the fingers and toes (typically involving fusion of the second, third, and fourth digits)

• Short, broad thumbs and big toes

Other Possible Features:

• Hearing loss

• Cleft palate

• Dental crowding or malocclusion

• Delayed speech and cognitive development (mild to moderate intellectual disability in some cases)

• Hydrocephalus (increased fluid in the brain) in severe cases

Diagnosis

Apert syndrome is usually diagnosed based on physical features at birth, followed by confirmatory genetic testing. Diagnostic steps include:

• Clinical examination: Identifies characteristic craniofacial and limb abnormalities

• Skull X-rays or CT scans: Show early fusion of cranial sutures

• Genetic testing: Confirms mutation in the FGFR2 gene

• Prenatal diagnosis: May be possible via ultrasound and genetic testing if there is a known family history

Treatment

Treatment for Apert syndrome is multidisciplinary and tailored to the individual’s needs. Early intervention can significantly improve function and quality of life. Treatment typically includes:

Surgical Management:

• Cranial surgery: Performed in infancy to relieve intracranial pressure and correct skull shape

• Facial surgery: Later in life to correct midface hypoplasia and improve breathing or appearance

• Hand and foot surgery: To separate fused digits and improve function

Therapies and Supportive Care:

• Speech therapy, physical therapy, and occupational therapy

• Early developmental intervention programs

• Dental and orthodontic care for jaw and tooth alignment

• Monitoring and management of hearing or vision issues

Prognosis

The prognosis for individuals with Apert syndrome depends on the severity of symptoms and access to medical care. With timely surgical and supportive interventions, many people with Apert syndrome can lead fulfilling lives.

• Most children benefit from early surgery and developmental therapies

• Cognitive development varies; some have normal intelligence while others may face learning difficulties

• Life expectancy is generally normal, though it may be reduced in severe cases with complications

Regular follow-up with a craniofacial team is essential to address the evolving medical and surgical needs of the individual.