Apert Syndrome (Apert's Syndrome)

Autosomal dominant - en[1]

Apert syndrome is a rare congenital disorder characterized by craniofacial anomalies, severe symmetrical syndactyly, and craniosynostosis


  • Raised intracranial pressure causing behavioral changes, frequent awakenings during the night (intracranial pressure rises during REM-sleep) and headaches in the morning.
  • Problems involving upper airway such as obstructive sleep apnea syndrome (OSAS), most frequently caused by midface hypoplasia, and stridor, due to craniosynostosis
  • Corneal injury and visual disturbances due to conjunctivitis and keratitis.
  • Level of intelligence ranges from normal to mental retardation.
  • Acrocephaly, flat occiput, brachycephaly, and prominent forehead are some of the features of the skull and head in such patients.
  • Common facial features during childhood are a break in the continuity of the eyebrows, maxillary hypoplasia, and trapezoid-shaped mouth at rest.
  • Low-set ears, with rare conductive hearing loss.
  • Hypertelorim, proptosis, strabismus, optic atrophy, down-slanting palpebral fissures, keratoconus, congenital glaucoma, preventable visual loss or blindness.
  • Depressed nasal bridge. Nose in such patient is also short and wide with parrot-beak appearance.
  • Mouth has prominent mandible, bifid uvula, cleft palate
  • Patients also suffer from orthodontic problems, including crowded upper teeth and ectopic eruption.
  • Generally the upper limbs are severely affected compared to the lower limbs. Syndactyly and brachydatyly are also observed.
  • Other associated conditions include atrial septal defect, pulmonary stenosis, ventricular septal defect, endocardial fibroelastosis, polycystic kidneys, hydronephrosis, vaginal atresia, clitoromegaly, pyrolic stenosis, ectopic anus, tracheoesophageal fistula, pulmonary aplasia.
  • Some of the common CNS malformations are ventriculomegaly, megalencephaly, hypoplastic cerebral white matter and heteroptopic gray matter. Progressive hydrocephalus is not common.
  • There are some skeletal and cartilaginous defects. Brittle nails, synonychia, hyperkeratosis, and paronychial infections are some of the other common symptoms [5] [6].


Laboratory studies

Since molecular mechanism in this disease is specific, molecular analysis is useful in such patients. 


  • Imaging studies of skull, spinal, limb, and hand radiography are beneficial. Craniosynostosis can be evaluated by skull radiography, while spinal radiography helps to determine spinal fusion, and other congenital features. 
  • CT scan: CT scan with comparative 3D reconstructional analysis of the calvaria is considered as the most useful imaging technique for the diagnosis of Apert syndrome.
  • MRI: Non-progressive ventriculomegaly, absence of septal leaflets, and deficiency of the corpus callosum can be detected by MRI. It also reveals spatial arrangements of the bones in the body [7] [8].


  • Medical care: Goal of management of Apert syndrome is to manage the symptoms of the condition. Cornea of the patient must be protected by instilling lubricants with bland ointments. The upper airway obstruction during the neonatal period can be managed by removing excess nasal secretions, applying nasal decongestants, treating upper airway infections, and humidification. For chronic middle-ear effusion, antimicrobial therapy is prescribed. The patient may also suffer from several psychological challenges which require emotional support. For obstructive sleep apnea syndrome, if treatment is indicated, adenotonsillectomy, nocturnal oxygen, continuous positive airway pressure (CPAP), or midface advancement are sufficient.
  • Surgical care: Severe corneal conditions can be managed by lateral tarsorrhaphy (which can protect the cornea and vision). Upper airway obstruction is treated by orotracheal intubation. To treat very severe cases of obstructive sleep apnea syndrome, tracheostomy is recommended. To prevent and/or treat raised intracranial pressure (ICP), patients should routinely undergo a cranial skull expansion in the first year of life. Screening for raised ICP with fundoscopy (to check for papilledema as a sign of raised ICP) is essential. Nasal surgery, mid-facial surgery and mandibular surgery are some of the surgical approaches available for the management of symptoms associated with Apert syndrome [9] [10] [11].
  • Follow-up: Regular follow-up includes measurements of head circumference (skull growth), fundoscopy to check for papilledema, polysomnography (to check for OSAS) and MRI (to check for ventriculomegaly/hydrocephalus and Chiari I malformation).


Surgery can assist the brain to develop normally, though there is a high chance of certain brain structures to remain poorly developed. Children with Apert syndrome, who are raised by the parents, develop higher intellectual ability. Though life expectancy in the children varies, those who have survived without any cardiac problems during their formative years can have normal or near-normal life expectancy.


Mental retardation, ocular hypertelorism, syndactyly, tarsal coalition, brachycephaly, craniosynostosis and bifid uvula are some of the complications of Apert syndrome.


The etiology of Apert syndrome involves the specific substitution mutation of the adjacent amino acid in the linker between second and third immunoglobulin domains of FGFR2 (in 98% of cases). More rarely, Apert syndrome can be caused by insertion mutations or deletions, in or near exon 9 of FGFR2.

The rarity of the cases can be attributed to the reduced genetic fitness. In this syndrome, family history is usually insignificant, though paternal age has an effect in the etiology of this disease; age of the father greater than 50 years causes an increase the chance of Apert syndrome [2].


Racial dispensation is observed in patients with Apert syndrome. While Asians have the highest prevalence of this disease, this syndrome is lowest amongst Hispanics. This disease can be observed early as the newborn may have morphological conditions such as syndatyly in the hands and feet [3].

Sex distribution
Age distribution


The genetic mutation in the FGFR2 gene involving the two adjacent amino acids causes Apert syndrome [4].


Genetic counseling can be of help if there is a family history of the syndrome.


Apert syndrome is a congenital disorder characterized by symptoms such as craniofacial anomalies, severe symmetrical syndactyly, and craniosynostosis. In such patients, the reproductive fitness is low. First described by a French physician in 1906, these cases arise due to a new and rare mutation. Apert syndrome may be inherited as an autosomal dominant trait or be sporadic, which results from new mutations with parental age effect [1].

Patient Information


Apert syndrome is the genetic disorder which manifests as abnormal development of the skull, and distorted shape of face and head. Most of the children have several birth defects. 


There is a rare and random mutation of the gene that causes Apert syndrome. Across the globe, only one in 65,000 babies is born with this disease.


Several symptoms are present in the patients with Apert syndrome. The defective gene allows the premature fusion of the skull bones known as craniosynostosis. The abnormal facial and skull growth leads to a head which is long, and have high forehead. Patients also have bulging eyes, and poor-closing eyes, with sunken middle face. Poor intellectual development, repeated ear, throat infections, obstructive sleep apnea, webbed hands or feet, and hearing loss are some other signs of the disease.


Genetic testing helps to identify the Apert syndrome. Imaging and laboratory studies can help diagnose Apert syndrome. 


Though there is no cure for Apert syndrome, surgery can help to manage the multiple problems that result from the disease. The goal of the managing Apert syndrome is the treatment of the symptoms of the disease.


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  1. Lajeunie E, Cameron R, El Ghouzzi V, et al. Clinical variability in patients with Apert's syndrome. J Neurosurg. Mar 1999;90(3):443-7.
  2. Coomaralingam S, Rothe P. Apert syndrome in a newborn infant without craniosynostosis. J Craniofac Surg. May 2012;23(3):e209-e211.
  3. Tolarova MM, Harris JA, Ordway DE, Vargervik K. Birth prevalence, mutation rate, sex ratio, parents' age, and ethnicity in Apert syndrome. Am J Med Genet. 1997 Nov 12;72(4):394-8.
  4. Ciasca SM. et al. Neuropsychological and Phonological Evaluation in the Apert’s syndrome. Arq Neuropsiquiatr 2001;59(2-B):342-6.
  5. Coomaralingam S, Rothe P. Apert syndrome in a newborn infant without craniosynostosis. J Craniofac Surg. May 2012;23(3):e209-e211.
  6. Hunt JA, Hobar PC. Common craniofacial anomalies: the facial dysostoses. Plast Reconstr Surg. 2002 Dec; 110(7):1714-25; quiz 1726; discussion 1727-8.
  7. Quintero-Rivera F, Robson CD, Reiss RE, et al. Apert syndrome: what prenatal radiographic findings should prompt its consideration?. Prenat Diagn. Oct 2006;26(10):966-72. 
  8. Quintero-Rivera F, Robson CD, Reiss RE, et al. Intracranial anomalies detected by imaging studies in 30 patients with Apert syndrome. Am J Med Genet A. Jun 15 2006;140(12):1337-8.
  9. Chen H. Apert syndrome. In: Springer; ed. Atlas of Genetic Diagnosis and Counseling. 2, Volume 1. New York Dordrecht Heidelberg London: 2012:119-133.
  10. Barnett S, Moloney C, Bingham R. Perioperative complications in children with Apert syndrome: a review of 509 anesthetics. Paediatr Anaesth. Jan 2011;21(1):72-7.
  11. Fearon JA, Podner C. Apert syndrome: evaluation of a treatment algorithm. Plast Reconstr Surg. Jan 2013;131(1):132-42

Media References

  1. Autosomal dominant - en, CC BY-SA 3.0