Apert Syndrome Clinical CharacteristicsOcular Features: In 10% of patients, keratitis and corneal scarring occur from the sometimes marked proptosis and corneal exposure. Optic atrophy is present in over 20% of patients. Strabismus, primarily exotropia, is found in more than 70% and various extraocular muscle anomalies may be detectable. Usually the exotropia has a V-pattern with overaction of the inferior oblique muscles while the superior oblique is weak. Amblyopia occurs in nearly 20%. The lid fissures often slant downward and the eyebrows may be interrupted. Systemic Features: This brachysphenocephalic type of acrocephaly is associated with syndactyly in the hands and feet. Pre- and postaxial polydactyly may be present. There is considerable variation in expression with some patients so mildly affected that they appear virtually normal, whereas others have extreme degrees of brachycephaly with high foreheads, midface hypoplasia, and proptosis secondary to shallow orbits. Imaging often reveals one or more CNS anomalies such as defects of the corpus callosum, partial absence of the septum pellucidum, ventriculomegaly, and sometimes hydrocephalus. A small but significant proportion of patients have some developmental delay and cognitive impairment. Over 39% of patients have a normal IQ. GeneticsThis type of craniosynostosis is caused by mutations in the fibroblast growth factor receptor-2 gene, FGFR2, located at 10q26.13. It is generally considered an autosomal dominant disorder based on familial cases but most occur sporadically. A paternal age effect on mutations has been found. The same gene is mutant in allelic disorders sometimes clinically separated and labeled Crouzon (123500) and Pfeiffer (some cases) (101600) syndromes. Jackson-Weiss syndrome (123150) maps to the same locus. However, this entire group has many overlapping features making classification on clinical grounds alone difficult. Only Apert syndrome is caused by mutations in a single gene whereas other syndromes seem to result from mutations in multiple genes. Pedigree: Autosomal dominantTreatmentTreatment Options: No specific treatment is available for this disorder but exposure keratitis may require surveillance and therapy. ReferencesArticle Title: Ophthalmic findings in apert syndrome prior to craniofacial surgery Khong JJ, Anderson P, Gray TL, Hammerton M, Selva D, David D. Ophthalmic findings in apert syndrome prior to craniofacial surgery. Am J Ophthalmol. 2006 Aug;142(2):328-30. PubMed ID: 16876521 The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm Glaser RL, Broman KW, Schulman RL, Eskenazi B, Wyrobek AJ, Jabs EW. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet. 2003 Oct;73(4):939-47. PubMed ID: 12900791 Crouzon Syndrome. A clinical and roentgencephalometric study Kreiborg S. Crouzon Syndrome. A clinical and roentgencephalometric study. Scand J Plast Reconstr Surg Suppl. 1981;18:1-198. PubMed ID: 6955940 Read more about Apert Syndrome
Ophthalmic findings in apert syndrome prior to craniofacial surgery Khong JJ, Anderson P, Gray TL, Hammerton M, Selva D, David D. Ophthalmic findings in apert syndrome prior to craniofacial surgery. Am J Ophthalmol. 2006 Aug;142(2):328-30. PubMed ID: 16876521
The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm Glaser RL, Broman KW, Schulman RL, Eskenazi B, Wyrobek AJ, Jabs EW. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet. 2003 Oct;73(4):939-47. PubMed ID: 12900791
Crouzon Syndrome. A clinical and roentgencephalometric study Kreiborg S. Crouzon Syndrome. A clinical and roentgencephalometric study. Scand J Plast Reconstr Surg Suppl. 1981;18:1-198. PubMed ID: 6955940
