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Apert syndrome

Synonym(s) ACS1
Acrocephalosyndactyly type 1
Prevalence 1-9 / 100 000
Inheritance Autosomal dominant
Age of onset Antenatal
  • Q87.0
  • C0001193
  • D000168
  • 10002943


Disease definition

Apert syndrome (AS) is a frequent form of acrocephalosyndactyly (see this term), a group of inherited congenital malformation disorders, characterized by craniosynostosis (see this term), midface hypoplasia, and finger and toe anomalies and/or syndactyly.


The estimated incidence of Apert syndrome is reported to be 1/100,000 to 1/160,000 live births.

Clinical description

Patients generally have extensive structural and functional impairments related to cranial and limb deformities. Craniosynostosis can lead to acrobrachycephaly or turribrachycephaly with delayed closure of fontanels and a possible impact on brain growth and neurological development. Macrocephaly is also found. Limb malformations mainly consist of soft tissue and bony syndactyly of fingers and toes (involving variable numbers of digits), occasional rhizomelic shortening, and elbow ankylosis, with functional impairments and restriction of mobility. Facial findings include midface hypoplasia that is generally moderate to severe with hypoplasia of the maxilla, shallow orbits, strabismus, hypertelorism, down-slanting palpebral fissures, and proptosis, as well as depressed nasal bridge and deviated nasal septum. Dental findings include delayed eruption, impaction, crowding, thick gingival swelling, and missing teeth, along with a high risk of caries. Unilateral and bilateral posterior crossbites are frequent. Common associated complications include chronic otitis media, hearing loss, and increased ocular pressure that can cause blindness. Moderate to severe intellectual disability and variable developmental delay are also common in AS (more than 50% of cases). Some patients are also reported to have agenesis of the corpus callosum, ventriculomegaly, hydrocephalus, fused cervical vertebrae (usually C5-C6), and occasionally, cardiac and gastrointestinal defects, radiohumeral synostosis, or cleft velum (see this term).


A mutation in the FGFR2 gene (10q25.3-10q26) involved in cell signaling during embryonic development is causative in Apert syndrome. Advanced paternal age has been associated with de novo mutations, which are found in most cases.

Diagnostic methods

Diagnosis is based on the clinical findings at birth. Some cases may be identified prenatally. The diagnosis can be confirmed by molecular genetic testing.

Differential diagnosis

The differential diagnosis includes other syndromic craniosynostosis syndromes, such as Pfeiffer, Crouzon, Saethre-Chotzen, Muenke, and Jackson-Weiss syndromes (see these terms).

Antenatal diagnosis

Prenatal MRI or molecular genetic testing can be used to diagnose suspected cases.

Genetic counseling

A mutation in the FGFR2 gene (10q25.3-10q26) involved in cell signaling during embryonic development is causative in Apert syndrome. Advanced paternal age has been associated with de novo mutations, which are found in most cases.

Management and treatment

A multidisciplinary approach to care is necessary with life-long monitoring. Treatment primarily involves craniosynostosis release, followed by surgical advancement or distraction for midface hypoplasia, and reparative or cosmetic treatment of other malformations. Successful treatment can improve aesthetics and functional performance (breathing, mastication, oral and ocular health). In patients with mitten-glove syndactyly, surgical separation of the digits generally provides little functional improvement. The psychosocial aspects of the syndrome should also be taken into account.


The prognosis is guarded. Many individuals have life-threatening complications, including airway and central nervous system compromise. Others can do relatively well with proper medical and surgical management, but intellectual limitations are still very common. Life expectancy varies among patients with AS due to variable clinical severity and treatment success.

Expert reviewer(s)

  • Dr Austin HAMM
  • Dr Nathaniel ROBIN

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