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

This disease is promted by the following process: hereditary.

Presentation

  • 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].

psychiatrical
Suggestibility
  • […] multiple types: type 1 - Noack syndrome; now classified with Pfeiffer syndrome type 2 - Carpenter syndrome type 3 - Sakati-Nyhan-Tisdale syndrome type 4 - Goodman syndrome; now classified with Carpenter syndrome type 5 - Pfeiffer syndrome It has been suggested[en.wikipedia.org]
  • Orthodontic treatment using braces will be suggested to improve overcrowding and speech.[gosh.nhs.uk]
  • Some research suggests that increased paternal age may be a risk factor.[gillettechildrens.org]
  • […] complex) Other features include: tower shaped head and prominent forehead hypertelorism mental retardation (IQ however can be normal) exopthalmos History and etymology It is named after Eugene Apert , French physician, in 1906 although some reports suggest[radiopaedia.org]
  • Some findings suggest that early neurosurgical intervention does not eliminate all risk for mental disability, some of which is thought to be related to subtle brain malformations. [chla.org]
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  • musculoskeletal
    Acrocephaly
    • As a result, the head tends to appear abnormally pointed at the top (acrocephaly) and the diameter from the front to the back of the skull (anterior-posterior diameter) may be shortened.[rarediseases.org]
    • Hypertelorism is exemplified with increased distance between the eyes; additionally, acrocephaly is noted with forehead broadening and skull flattening.[orthobullets.com]
    • McKusick , OMIM, Johns Hopkins University , December 27, 2006 Gene Map Locus: 10q26 Apert (1906) defined a syndrome characterized by skull malformation (acrocephaly of brachyshenocephalic type) and syndactyly of the hands and feet of a special type (complete[ibis-birthdefects.org]
    • Once there is damage to the cornea, it will lead to infection such as conjunctivitis and keratitis Mental retardation Physical Abnormalities Skull and Face Craniostenosis affecting most commonly the coronal sutures which may lead to the development of acrocephaly[syndrome.org]
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  • Entire body system
    Physician
    • Apert syndrome is named for the French physician who first described it, E.[apert.org]
    • Chris and Kerry rely on Fearon and his staff to help manage their select team of physicians, therapists and other health professionals located in the Chicago area.[chicagoparent.com]
    • Depending on the type of medical professional diagnosing, typically the DSM-V (standard classification of mental disorders used by mental health professionals in the U.S.) is used to diagnose by primary care physicians, neurologists, and psychiatrists[news-medical.net]
    • Snoring problems should be followed up by a physician.[mun-h-center.se]
    • […] facial hypoplasia limb syndactyly (tends to be complex) Other features include: tower shaped head and prominent forehead hypertelorism mental retardation (IQ however can be normal) exopthalmos History and etymology It is named after Eugene Apert , French physician[radiopaedia.org]
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  • 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].

    Pathology

    Biopsy
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  • Laboratory

    Serum
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  • 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.

    Complications

    Ventricular Septal Defect
    • […] aorta – in this situation, the aorta is situated directly over a ventricular septal defect Coarctation of the aorta – the aorta narrows on the area of insertion of the ductus arteriosus Dextrocardia – the heart is situated on the right side of the body[syndrome.org]
    • However, affected children do have a much higher incidence of small holes in their hearts called ASD’s (atrial septal defects) and VSD’s (ventricular septal defects).[thecraniofacialcenter.com]
    Acrocephalopolysyndactyly
    • It has several different types: type 1 - Apert syndrome type 2 - Crouzon syndrome type 3 - Saethre-Chotzen syndrome type 5 - Pfeiffer syndrome A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation[en.wikipedia.org]
    Polydactyly
    • It has several different types: type 1 - Apert syndrome type 2 - Crouzon syndrome type 3 - Saethre-Chotzen syndrome type 5 - Pfeiffer syndrome A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation[en.wikipedia.org]
    • Less commonly, people with this condition may have extra fingers or toes (polydactyly).[slideshare.net]
    • Less commonly, people with this condition may have extra fingers or toes ( polydactyly ).[ghr.nlm.nih.gov]
    • In addition, a varied number of fingers and toes are fused together (syndactyly) with, on the rare occasion, extra fingers or toes (polydactyly).[rainbowkids.com]
    Crouzon Syndrome
    • Crouzon syndrome (CS) .[forgottendiseases.org]
    • It has several different types: type 1 - Apert syndrome type 2 - Crouzon syndrome type 3 - Saethre-Chotzen syndrome type 5 - Pfeiffer syndrome A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation[en.wikipedia.org]
    • Crouzon syndrome, in comparison, occurs in about 1 out of 25,000 live births [1-4].[eyewiki.aao.org]
    • Bicoronal synostosis, or brachycephaly, is the suture fusion found most often in Apert's (and Crouzon's) syndromes, these children also often have fusion of the sutures of the skull base.[skullbaseinstitute.com]
    • Different mutations in FGFR2 are also responsible for two other similar genetic diseases, namely, Pfeiffer syndrome and Crouzon syndrome.[medicinenet.com]
    Apert Syndrome
    • Apert Syndrome Treatments Apert syndrome has no known cure.[webmd.com]
    • Chen H: Apert syndrome.[link.springer.com]
    • Articles Related to Apert Syndrome Resources for Apert Syndrome Apert Syndrome Adoption - Facebook Group Children's Craniofacial Association[rainbowkids.com]
    Syndactyly
    • Simple syndactyly of the small and ring fingers is present.[boneandspine.com]
    • The syndactyly may involve soft tissues only (cutaneous syndactyly) or include fusion of bone (osseous syndactyly).[rarediseases.org]
    • "Syndactyly correction of the hand in Apert syndrome".[en.wikipedia.org]
    • Syndactyly in AS Severe syndactyly of the hands and feet is a consistent and cardinal feature of Apert syndrome.[forgottendiseases.org]
    • Corrective hand surgery in the form of syndactyly release and grafting was performed for right upper limb.[ijri.org]
    Craniosynostosis
    • In addition to isolated craniosynostosis, there are also a number of craniosynostosis syndromes .[forgottendiseases.org]
    • Both genetic and environmental factors contribute to craniosynostosis.[sickkids.ca]
    • Both single suture craniosynostosis and craniosynostosis syndromes are diagnosed through physical examination at birth.[craniofacialcenter.ucsf.edu]
    • Cohen MM Jr: Genetic perspectives on craniosynostosis and syndromes with craniosynostosis.[link.springer.com]
    Congenital Abnormality
    • Depending on the severity of Apert's syndrome and the associated congenital abnormalities, other operations such as rhinoplasty - plastic surgery of the nose, genioplasty - plastic surgery of the chin, eye muscle surgery to correct strabismus or eyelid[skullbaseinstitute.com]

    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.

    Other symptoms

    Normal
    • Those with Apert syndrome who survive past childhood and don't have heart problems likely have a normal or near-normal life expectancy.[webmd.com]
    • The infant had a normal spine, 12 paired ribs, and a normal shoulder girdle and pelvis.[pediatricsconsultantlive.com]
    • The bones of jaw and cheeks are modified and brought forward to normal position.[diseasespictures.com]
    • But now that I have this thing off, I can sleep normally."[wdrb.com]
    • However, others are able to develop normal intellectual abilities.[choc.org]
    No Development
    • Other method of treatment depends on development of symptoms.[diseasespictures.com]
    • Abnormal growth patterns develop as the soft sutures of the skull close in an untimely manner.[craniofacial.net]
    • Apert syndrome is a genetic disorder that causes abnormal development of the skull.[webmd.com]
    • Even with optimal timing, some brain structures may not develop normally.[smartspeechtherapy.com]
    • Early fusion of the skull bones also affects the development of the brain, which can disrupt intellectual development.[slideshare.net]
    Birth
    • Initially it was reported to be only 1 case in every 200,000 live births.[epainassist.com]
    • They also found that the changes in suture closure in the head progressed from 17.5 days to birth, so that the heads of newborn mice looked very different at birth than they did when first imaged prenatally.[news.psu.edu]
    • However this is a rare disorder that occurs in one out of million births.[diseasespictures.com]
    • Paternal age effect is demonstrable ... 57 cases gave a birth prevalence calculated to be approximately 15.5 per million births, ...[ibis-birthdefects.org]
    • Apert syndrome affects about one of every 100,000 births and varies less from case to case than Crouson and Pfeiffer.[craniofacialcenter.ucsf.edu]
    Acrocephalosyndactyly
    • Acrocephalosyndactylia (or acrocephalosyndactyly) is the common presentation of craniosynostosis and syndactyly.[en.wikipedia.org]
    • APERT’S SYNDROME ( acrocephalosyndactyly ) Autosomal Dominant.[fetalultrasound.com]
    • Apert syndrome (also known as type I acrocephalosyndactyly ) is a syndrome that is predominantly characterised by skull and limb malformations.[radiopaedia.org]
    • Other features of acrocephalosyndactyly may include shallow bony orbits and broadly spaced eyes.[en.wikipedia.org]
    Congenital
    • Risk factors increased paternal age has been proposed 6 Associations CNS anomalies congenital cardiac anomalies (10%) congenital genitourinary anomalies symphalangism There are many of which the classic triad includes 3 : craniofacial craniosynostosis[radiopaedia.org]
    • Goldberg et al review congenital hand conditions and the malformations associated with them.[orthobullets.com]
    • […] narrows on the area of insertion of the ductus arteriosus Dextrocardia – the heart is situated on the right side of the body instead of its normal orientation which is slightly pointing to the left Tetralogy of Fallot – this is a combination of four congenital[syndrome.org]
    • Apert syndrome is a form of acrocephalosyndactyly , a congenital disorder characterized by malformations of the skull, face, hands and feet.[en.wikipedia.org]
    Saethre-Chotzen Syndrome
    • It has several different types: type 1 - Apert syndrome type 2 - Crouzon syndrome type 3 - Saethre-Chotzen syndrome type 5 - Pfeiffer syndrome A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation[en.wikipedia.org]
    • The differential includes other forms of acrocephalosyndactyly and acrocephalopolysynactyly : Saethre-Chotzen syndrome Pfeiffer syndrome Carpenter syndrome Crouzon syndrome 1.[radiopaedia.org]
    • These similar syndromes include: Carpenter syndrome (kleeblattschadel, cloverleaf skull deformity) Crouzon disease (craniofacial dysostosis) Pfeiffer syndrome Saethre-Chotzen syndrome The health care provider will perform a physical exam.[medlineplus.gov]
    • These similar syndromes include: Carpenter syndrome (kleeblattschadel, cloverleaf skull deformity) Crouzon disease (craniofacial dysostosis) Pfeiffer syndrome Saethre-Chotzen syndrome Exams and Tests The health care provider will perform a physical exam[uichildrens.org]
    • The diagnosis of Apert, Crouzon, Pfeiffer and Saethre-Chotzen Syndromes is based on clinical findings, although there is considerable clinical overlap.[sickkids.ca]
    Development Normal
    • However, others are able to develop normal intellectual abilities.[choc.org]
    • As an fetus's brain continues to grow and develop, normal joints allows for the uniform expansion of the brain.[study.com]
    • Call your provider if you have a family history of Apert syndrome or you notice your baby's skull is not developing normally.[medlineplus.gov]
    • Support Groups Children's Craniofacial Association: www.ccakids.com When to Contact a Medical Professional Call your provider if you have a family history of Apert syndrome or you notice your baby's skull is not developing normally.[uichildrens.org]
    • This early fusion of the skull prevents it from developing normally, and causes the child to have an unusual head and face shape.[childrens.com]
    Severe Syndactyly
    • ., Suite 2506 Montreal, Québec, H2   3P7 Canada E-mail: [email protected] Abstract Apert syndrome or acrocephalosyndactyly is a rare autosomal dominant malformation syndrome characterized by craniosynostosis, symmetric severe syndactyly, and[onlinelibrary.wiley.com]
    • Syndactyly in AS Severe syndactyly of the hands and feet is a consistent and cardinal feature of Apert syndrome.[forgottendiseases.org]
    • The primary deformity of the hands and feet is severe syndactyly, often with fusion of the digits.[orthobullets.com]
    • The S252W mutation is more commonly associated with cleft palate and craniofacial deformity, whereas the P253R mutation is more commonly associated with severe syndactyly .7 Apert syndrome can be diagnosed in utero with ultrasonography; however, it is[pediatricsconsultantlive.com]
    No Polydactyly
    • It has several different types: type 1 - Apert syndrome type 2 - Crouzon syndrome type 3 - Saethre-Chotzen syndrome type 5 - Pfeiffer syndrome A related term, "acrocephalopolysyndactyly" (ACPS), refers to the inclusion of polydactyly to the presentation[en.wikipedia.org]
    • Less commonly, people with this condition may have extra fingers or toes (polydactyly).[slideshare.net]
    • Less commonly, people with this condition may have extra fingers or toes ( polydactyly ).[ghr.nlm.nih.gov]
    • In addition, a varied number of fingers and toes are fused together (syndactyly) with, on the rare occasion, extra fingers or toes (polydactyly).[rainbowkids.com]

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    References

    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

    • Apert's syndrome (a type of acrocephalosyndactyly)–observations on a British series of thirty‐nine cases* - CE Blank - Annals of human genetics, 1959 - Wiley Online Library
    • Associated malformations and chromosomal anomalies in 42 cases of prenatally diagnosed diaphragmatic hernia - I Witters, E Legius, P Moerman - American journal of , 2001 - Wiley Online Library


    Media References

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