Edit concept Question Editor Create issue ticket

Apert Syndrome

Apert's Syndrome

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


Presentation

Anisocoria
  • Very soon after completion of surgery an anisocoria (unilateral dilation of a pupil) was noticed. This was followed by intracranial oedema which was fatal. The aetiology was dissection of the right internal carotid artery is reported.[ncbi.nlm.nih.gov]
Short Arm
  • The X-Y homologous gene amelogenin maps to the short arms of both the X and Y chromosomes and is highly conserved in primates. Genomics 14, 203–205 (1992). 54 Miki, T. et al.[doi.org]
Hearing Impairment
  • 80%-99% of people have these symptoms Acrobrachycephaly 0004487 Brachyturricephaly High, prominent forehead 0000244 Broad forehead Increased width of the forehead Wide forehead [ more ] 0000337 Conductive hearing impairment Conductive deafness Conductive[rarediseases.info.nih.gov]
  • In nine others, it was not possible to determine whether there was any congenital hearing impairment. Figure 1 Congenital hearing impairment profile. In this study, 65 had documented otitis media with effusion at least once.[adc.bmj.com]
  • Children with Apert syndrome may have mental deficiencies, short stature, hearing impairment, frequent ear infections, prominent and/or bulging eyes, a large or late-closing soft spot on the skull,dental anomalies, and other skeletal and congenital abnormalities[consultant360.com]
  • Hearing Loss - Some individuals with Apert's suffer with hearing impairments and/or hearing loss due to persistent build up of fluids and chronic ear infections. Obstructive Sleep Apnea - Malformation of facial bones can lead to breathing problems.[study.com]
Hypertelorism
  • Prenatal ultrasound diagnosis is based on the detection of abnormal cranial shape, midfacial hypoplasia and bilateral syndactyly of hands and feet, hypertelorism, and exorbitism.[ncbi.nlm.nih.gov]
  • Abstract Apert syndrome is characterized by hypertelorism, a negative canthal axis, and central midfacial hypoplasia, resulting in a biconcave face. Bipartition distraction partially corrects these facial anomalies.[ncbi.nlm.nih.gov]
  • The patient presented with several craniofacial deformities, including brachycephaly, midface hypoplasia, flat face, hypertelorism, ocular proptosis, downslanting palpebral fissures.[ncbi.nlm.nih.gov]
  • The patient presented with several craniofacial deformities, including severe brachycephaly, midface hypoplasio, flat forehead, proptosis, hypertelorism, and short nose with a bulbous tip. Syndactylies of the hands and feet were also observed.[ncbi.nlm.nih.gov]
  • We report a case of an 11-year-old girl presenting with Apert syndrome characterized by midface concavity, protrusion of the eyeballs, and ocular hypertelorism.[ncbi.nlm.nih.gov]
Beaked Nose
  • Agenesis of corpus callosum 0001274 Aplasia/Hypoplasia of the thumb Absent/small thumb Absent/underdeveloped thumb [ more ] 0009601 Broad thumb Broad thumbs Wide/broad thumb [ more ] 0011304 Cervical C5/C6 vertebrae fusion 0004635 Convex nasal ridge Beaked[rarediseases.info.nih.gov]
  • The head is unable to grow normally, which leads to a sunken appearance in the middle of the face, bulging and wide-set eyes, a beaked nose, and an underdeveloped upper jaw leading to crowded teeth and other dental problems.[craniofacialmd.com]
  • Craniosynostosis (premature closure of the sutures of the skull) causing the head to have a tall, “domed” appearance (also known as turribrachycephaly) Flat midface Wide set and bulging eyes Beaked nose Syndactyly of fingers and toes (fusion of the skin[nicklauschildrens.org]
Meningism
  • […] frequently function galactose galactosemia Gaucher's disease genetic globoid hemispheres hemorrhages Hurler's syndrome hydrocephalus idiocy incidence increased infantile infants infection intracranial involvement lesions lipid malformations maternal meningitis[books.google.com]

Workup

Laboratory studies

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

Imaging 

  • 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].
Posterior Fossa Cysts
  • fossa cyst in communication with the fourth ventricle on axial images, digital fusion, and bilateral syndactyly of the hands and feet.[ncbi.nlm.nih.gov]
  • fossa cyst 0007291 Pyloric stenosis 0002021 Shallow orbits Decreased depth of eye sockets Shallow eye sockets [ more ] 0000586 Synostosis of carpal bones Fusion of wrist bones 0005048 Vaginal atresia Abnormally closed or absent vagina 0000148 Ventricular[rarediseases.info.nih.gov]

Treatment

  • 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).

Prognosis

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.

Complications

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

Etiology

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].

Epidemiology

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

Pathophysiology

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

Prevention

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

Summary

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

Definition

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. 

Cause 

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.

Symptoms

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.

Diagnosis

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

Treatment

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.

References

Article

  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

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 21:59