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.
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.
