Apert Syndrome 

Updated: Aug 21, 2018
Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Maria Descartes, MD 

Overview

Background

Apert syndrome is a rare autosomal dominant disorder characterized by craniosynostosis, craniofacial anomalies, and severe symmetrical syndactyly (cutaneous and bony fusion) of the hands and feet (see the images below). It is probably the most familiar and best-described type of acrocephalosyndactyly. Reproductive fitness is low, and more than 98% of cases arise by new mutation.The syndrome is named for the French physician who described the syndrome acrocephalosyndactylia in 1906.[1]

An infant with Apert syndrome is shown. Note the c An infant with Apert syndrome is shown. Note the characteristic ocular hypertelorism, down-slanting palpebral fissures, proptotic eyes, horizontal groove above the supraorbital ridge, break of the eyebrows' continuity, depressed nasal bridge, and short, wide nose with bulbous tip.
Note the mitten appearance of the hands with synda Note the mitten appearance of the hands with syndactyly involving the second, third, fourth, and fifth fingers. This patient also has characteristic concave palms, hitchhiker posture (radial deviation) of the short broad thumbs, and contiguous nail beds (synonychia).
Note the socklike appearance of the feet with synd Note the socklike appearance of the feet with syndactyly involving the second, third, fourth, and fifth toes. The patient also has contiguous nail beds (synonychia).
In this profile photo, turribrachycephaly (high pr In this profile photo, turribrachycephaly (high prominent forehead), proptosis, a depressed nasal bridge, a short nose, and low-set ears are prominent.
This radiograph demonstrates turribrachycephaly, s This radiograph demonstrates turribrachycephaly, shallow orbits, ocular hypertelorism, and a hypoplastic maxilla.
Note the osseous syndactyly involving the second, Note the osseous syndactyly involving the second, third, fourth, and fifth fingers; multiple synostosis involving the distal phalanges and proximal fourth and fifth metacarpals; symphalangism of the interphalangeal joints; shortening and radial deviation of the distal phalanx; and the delta-shaped deformity of proximal phalanx of the thumbs.
Note the osseous syndactyly, fusion of the interph Note the osseous syndactyly, fusion of the interphalangeal joints, synostosis involving the proximal first and second metatarsals, and the partially duplicated and delta-shaped proximal phalanx of the great toes.

 

Pathophysiology

During early infancy (< 3 mo), the coronal suture area is prematurely closed. A bony condensation line beginning at the cranial base and extending upward with a characteristic posterior convexity represents this occurrence. Anterior and posterior fontanelles are widely patent. The midline of the calvaria has a gaping defect, extending from the glabellar area to the posterior fontanelle via the metopic suture area, anterior fontanelle, and sagittal suture area. The skull with a gaping midline defect appears to permit adequate accommodation of the growing brain. The lambdoidal sutures appear normal in all cases.

During the first 2-4 years of life, the midline defect is obliterated by coalescence of the enlarging bony islands without evidence of any proper formation of sutures. An extreme short squama and orbital part of the frontal bone together with the posterior convexity of the coronal bone condensation line suggest that growth inhibition in the sphenofrontal and coronal suture area has its onset very early in fetal life.

Unique fibroblast growth factor receptor 2 (FGFR2) mutations lead to an increase in the number of precursor cells that enter the osteogenic pathway. Ultimately, this leads to increased subperiosteal bone matrix formation and premature calvaria ossification during fetal development. The order and rate of suture fusion determine the degree of deformity and disability. Once a suture becomes fused, growth perpendicular to that suture becomes restricted, and the fused bones act as a single bony structure. Compensatory growth occurs at the remaining open sutures to allow continued brain growth; however, complex, multiple sutural synostosis frequently extends to premature fusion of the sutures at the base of the skull, causing midfacial hypoplasia, shallow orbits, a foreshortened nasal dorsum, maxillary hypoplasia, and occasional upper airway obstruction.

A retrospective study by Kolar et al examined the characteristics of mandibular growth associated with FGFR2 mutations, including in children with Apert, Crouzon, or Pfeiffer syndrome, with initial measurements finding slightly greater than normal mandibular height and bigonial breadth and deficient sagittal depth and cranial base width. Slight early growth acceleration was found along the vertical and sagittal axes, while growth was deficient at the cranial base. The mature skeleton was marked by above average mandibular vertical height and bigonial width, with deficiency still found in the mandibular depth (forward sagittal growth) and cranial base width.[2]

The first genetic evidence that syndactyly in Apert syndrome is a keratinocyte growth factor receptor (KGFR)-mediated effect was provided by the observation of the correlation between KGFR expression in fibroblasts and severity of syndactyly. Patients with Ser252Trp and those with Pro253Arg have different phenotypic expression. The syndactyly is more severe with Pro253Arg mutation for both hands and feet, whereas cleft palate is significantly more common with Ser252Trp mutation.[3]

Amblyopia and strabismus are more common in patients with the FGFR2 Ser252Trp mutation, and optic disc pallor is more frequent in patients with the FGFR2 Pro253Arg mutation.[4] Patients with FGR2 Ser252Trp mutations have a significantly greater prevalence of visual impairment compared with patients with the FGFR2 Pro253Arg mutation.[4, 5]

Epidemiology

Frequency

United States

  • Prevalence is estimated at 1 in 65,000 (approximately 15.5 in 1,000,000) live births.[6, 7]

  • Apert syndrome accounts for 4.5% of all cases of craniosynostosis.

Mortality/Morbidity

See the list below:

  • Most patients experience some degree of upper airway obstruction during infancy. Upper airway compromise due to reduction in nasopharynx size and choanal patency as well as lower airway compromise due to anomalies of the tracheal cartilage may be responsible for early death.

  • Sleep apnea syndrome is common. Upper airway compromise, consisting of obstructive sleep apnea and cor pulmonale, may result from small nasopharyngeal and oropharyngeal dimension in the Apert craniofacial configuration.

  • Patients are at risk for complications resulting from elevated intracranial pressure despite surgical attempts to increase cranial capacity in infancy.

Race

See the list below:

  • Asians have the highest prevalence (22.3 cases per million live births).

  • Hispanics have the lowest prevalence (7.6 cases per million live births).

Sex

See the list below:

  • Apert syndrome has no sex predilection.

Age

See the list below:

  • Apert syndrome is detected in the newborn period due to craniosynostosis and associated findings of syndactyly in the hands and feet.

 

Presentation

History

See the list below:

  • Family history is usually not significant because most cases of Apert syndrome are sporadic. A paternal age effect increases in fathers older than 50 years.

  • Headache and vomiting are signs of acute increased intracranial pressure, especially in cases of multiple suture involvement.

  • Stridor and sleep apnea indicate problems with the upper airway, resulting from craniosynostosis of sutures of the base of the skull.

  • Visual disturbance can result from corneal injury due to exposed conjunctivitis and keratitis.

  • Many patients exhibit mental retardation, although patients with normal intelligence have been reported.

Physical

Skull and face

With craniosynostosis, coronal sutures most commonly are involved, resulting in acrocephaly, brachycephaly, turribrachycephaly, flat occiput, and high prominent forehead.

A case of Apert syndrome, confirmed by molecular genetic analysis, was observed in a newborn infant who did not have craniosynostosis at birth. Because this disturbance in osteogenesis may vary in timing and extent, the diagnosis of Apert syndrome should be considered even in the absence of this hallmark finding.[8]

Other characteristics include the following:

  • Large late-closing fontanels are observed
  • A gaping midline defect is present
  • A rare cloverleaf skull anomaly is present in approximately 4% of infants
  • Common facial features during infancy include horizontal grooves above the supraorbital ridges that disappear with age, a break in the continuity of the eyebrows, and a trapezoid-shaped mouth at rest
  • A flattened, often asymmetrical face is observed
  • Maxillary hypoplasia with retruded midface is present

Ears, eyes, nose, and mouth

Patients have apparent low-set ears with occasional conductive hearing loss and congenital fixation of stapedial footplate.

Eyes exhibit down-slanting palpebral fissures, hypertelorism, shallow orbits, proptosis, exophthalmos, strabismus, amblyopia, optic atrophy, and, rarely, luxation of the eye globes, keratoconus, ectopic lentis, congenital glaucoma, lack of pigment in the fundi with occasional papilledema, and preventable visual loss or blindness.

A study by Forte et al found that in both Crouzon and Apert syndrome, the bony orbit is shortened, orbital and orbital soft-tissue volumes are reduced, and the globe’s volume is increased. In the study, which included 10 children with Apert syndrome, nine children with Crouzon syndrome, and 12 controls, the length of the bony orbit was 12% and 17% shorter in the Apert and Crouzon syndrome patients, respectively; the bony orbital volume was 21% and 23% smaller, respectively; the globe’s volume was 15% and 36% larger, respectively; and the orbital soft-tissue volume was 19% and 29% less, respectively.[9]

The nose has a markedly depressed nasal bridge. It is short and wide with a bulbous tip, parrot-beaked appearance, and choanal stenosis or atresia.

The mouth area has a prominent mandible, down-turned corners, high arched palate, bifid uvula, and cleft palate.

Orthodontic problems include crowded upper teeth, malocclusion, delayed dentition, ectopic eruption, shovel-shaped incisors, supernumerary teeth, V-shaped maxillary dental arch, bulging alveolar ridges, dentitio tarda, some impaction, partial eruption, idiopathic root resorption, transposition or other aberrations in the position of the tooth germs, and severe crowding.[10]

Extremities and digits

The upper limbs are more severely affected than lower limbs. Coalition of distal phalanges and synonychia found in the hands is never present in the feet. The glenohumeral joint and proximal humerus are more severely affected than the pelvic girdle and femur. The elbow is much less severely involved than the proximal portion of the upper limb.

Syndactyly involves the hands and feet with partial-to-complete fusion of the digits, often involving second, third, and fourth digits. These are often termed mitten hands and sock feet. In severe cases, all digits are fused, with the palm deeply concave and cup-shaped and the sole supinated.

Characteristics also include the following:

  • Hitchhiker posture or radial deviation of short or broad thumbs results from abnormal proximal phalanx
  • Brachydactyly occurs [11]
  • Nailbeds are contiguous (synonychia)
  • Some patients have subacromial dimples and elbow dimples during infancy
  • Mobility at the glenohumeral joint is limited with progressive limitation in abduction, forward flexion, and external rotation with growth
  • Limited elbow mobility is common with decreased elbow extension, flexion, pronation, and supination
  • Short humeri are a constant finding beyond infancy
  • Limited genu valga is present in many cases

Central nervous system

Intelligence varies from normal to mental deficiency, although a significant number of patients are mentally retarded. Malformations of the central nervous system (CNS) may be responsible for most cases.

Common CNS malformations include megalencephaly, agenesis of the corpus callosum, malformed limbic structures, variable ventriculomegaly, encephalocele, gyral abnormalities, hypoplastic cerebral white matter, pyramidal tract abnormalities, and heterotopic gray matter. In a study of 94 patients with Apert syndrome, Breik et al found the main CNS abnormalities to also include prominent convolutional markings (67%), a crowded foramen magnum (36%), and a deficient septum pellucidum (13%).[12] Progressive hydrocephalus is uncommon.

Papilledema and optic atrophy with loss of vision may be present in cases of subtle increased intracranial pressure.

Other skeletal and cartilaginous segmentation defects

These include the following:

  • Congenital cervical spinal fusion (68%), especially C5-C6
  • Aplasia or ankylosis of shoulder, elbow, and hip joints
  • Tracheal cartilage anomalies
  • Rhizomelia

Skin

Cutaneous characteristics include the following:

  • Hyperhidrosis (common)
  • Synonychia
  • Brittle nails
  • Acneiform lesions (frequent after adolescence)
  • Interruption of the eyebrows
  • Hypopigmentation
  • Hyperkeratosis in the plantar surface
  • Paronychial infections (more common in feet than hands and in patients who are institutionalized patients)
  • Excessive skin wrinkling of forehead
  • Skin dimples at knuckles, shoulders, and elbows

Cardiovascular (10%)

Cardiovascular characterstics include the following:

Genitourinary

Genitourinary characteristics (9.6%) include the following:

  • Duplication of renal pelvis
  • Hydronephrosis
  • Stenosis of bladder neck
  • Bicornuate uterus
  • Vaginal atresia
  • Protuberant labia majora
  • Clitoromegaly

Gastrointestinal

Gastrointestinal (GI) characteristics (1.5%) include the following:

  • Pyloric stenosis
  • Esophageal atresia and tracheoesophageal fistula
  • Ectopic or imperforate anus
  • Partial biliary atresia with agenesis of gallbladder

Respiratory

Respiratory characteristics (1.5%) include the following:

  • Anomalous tracheal cartilage
  • Tracheoesophageal fistula
  • Pulmonary aplasia
  • Absent right middle lobe of lung
  • Absent interlobular lung fissures

Causes

See the list below:

  • More than 98% of cases with Apert syndrome are caused by specific missense substitution mutations, involving adjacent amino acids (ie, Ser252Trp, Ser252Phe, Pro253Arg) in the linker between the second and third extracellular immunoglobulin domains of FGFR2, which maps to chromosome bands 10q26. The remaining cases are due to Alu-element insertion mutations in or near exon 9 of FGFR2.

  • Most cases are sporadic, resulting from new mutations with a paternal age effect. The incidence of FGFR2 mutations increases exponentially with paternal age, probably due to an increase in the frequency of these mutations and a selective advantage in the male germ line.[13, 14]

  • Most new mutations, estimated at 1 per 65,000 live births, imply that germline transversion rates at these 2 positions are currently the highest known in the human genome. The rarity of familial cases can be explained by reduced genetic fitness of individuals because of severe malformations and the presence of mental retardation in many cases.

 

DDx

Diagnostic Considerations

Mutations of the human FGFR s have also been identified as the cause of other craniosynostosis syndromes, including Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Beare-Stevenson syndrome, cutis gyrata, Antley-Bixler syndrome, and Muenke syndrome, as well as skeletal dysplasias such as achondroplasia and thanatophoric dysplasia. These conditions are described as follows[15, 16, 17, 18, 19, 20, 21] :

  • Beare-Stevenson syndrome (OMIM 123790): Patients present with mental retardation and associated cutaneous disorders, including cutis gyrata and acanthosis nigricans; patients with Beare-Stevenson syndrome may have FGFR2 mutations

  • Carpenter syndrome (OMIM 201000): This condition is autosomal recessive; patients present with a peculiar face, absence of osseous fusion of hand bones, and preaxial polydactyly of hands, feet, or both

  • FGFR3 -associated coronal synostosis syndrome: Patients present with variable clinical presentation overlapping with Pfeiffer, Jackson-Weiss, or Saethre-Chotzen syndrome phenotypes; some individuals with a disease-causing mutation may have no clinical problems

  • Jackson-Weiss syndrome (OMIM 123150): Patients present with enlarged or broad great toes with varus deviation and tarsal or metatarsal fusion, lack of thumb abnormalities, and craniofacial features, suggesting Pfeiffer syndrome; patients may have FGFR2 mutations

  • Pfeiffer syndrome (OMIM 101600): Patients present with hand and foot abnormalities characterized by broad thumbs and halluces with occasional cutaneous syndactyly; they also exhibit mild cranial deformities and lack of osseous fusion of the phalanges; approximately 67% of patients with Pfeiffer syndrome have identifiable mutations in FGFR1 and FGFR2

  • Saethre-Chotzen syndrome (OMIM 101400): Patients exhibit characteristic facies, relatively mild cranial deformity, and lack of osseous fusion of the hand bones; approximately 75% of patients with Saethre-Chotzen syndrome have identifiable mutations in the TWIST gene

Differential Diagnoses

 

Workup

Laboratory Studies

See the list below:

  • Molecular analysis of Apert syndrome

    • The molecular mechanism is exquisitely specific with a narrow mutational spectrum.

    • More than 98% of cases are caused by specific missense substitution mutations, involving adjacent amino acids (Ser252Trp, Ser252Phe, or Pro253Arg) in exon 7 of FGFR2.

    • The remaining cases are due to Alu-element insertion mutations in or near exon 9.

Imaging Studies

See the list below:

  • Skull radiography

    • Skull radiography can be performed to evaluate for craniostenosis, which usually involves coronal sutures and maxillary hypoplasia.

    • Abnormalities include sclerosis of suture line, bony bridging and beaking along the suture line, an indistinct suture line, turribrachycephaly, shallow orbits, and hypoplastic maxillae.

  • Spinal radiography

    • Spinal fusions, most commonly at the levels of C3-4 and C5-6, appear to be progressive and occur at the site of subtle congenital anomalies. They may not be apparent as congenital features.

    • Small-sized vertebral body and reduced intervertebral disc space are indicators of subsequent bony fusion.

  • Limb radiography: Radiographs of the limbs depict multiple epiphyseal dysplasia, short humeri, and glenoid dysplasia.

  • Hand radiography

    • Radiography of the hands can be performed to evaluate for cutaneous and osseous syndactyly.

    • The characteristic finding is complete syndactyly involving the second and fifth digits (mitten hands).

    • Multiple progressive synostosis involves distal phalanges, proximal fourth and fifth metacarpals, capitate, and hamate.

    • Symphalangism of interphalangeal joints is progressive.

    • Radiography of the distal phalanx reveals shortened and radial deviation.

    • Radiography of the proximal phalanx of the thumbs reveals delta-shaped deformity.

  • Foot radiography

    • Radiography of the feet can be performed to evaluate for cutaneous and osseous syndactyly. The characteristic finding is complete syndactyly involving the second and fifth digits (sock feet).

    • Fusion of tarsal bones, metatarsophalangeal and interphalangeal joints, and adjacent metatarsals

    • Delta-shaped proximal phalanx of the first toes

    • Occasional partial or complete duplication of the proximal phalanx of the great toes and first metatarsals

  • CT scanning

    • CT with comparative 3-dimensional reconstruction analysis of the calvaria and cranial bases has become the most useful radiological examination in identifying skull shape and presence or absence of involved sutures.

    • CT can precisely reveal the pathological anatomy and permit specific operative planning.

  • MRI

    • MRI reveals the anatomy of the soft-tissue structures and associated brain abnormalities (ie, nonprogressive ventriculomegaly; hydrocephalus; complete or partial absence of the septum pellucidum; absence of septal leaflets; and thinning, deficiency, or agenesis of the corpus callosum).[22, 23]

    • MRI can also reveal spatial arrangement of the bones.

Other Tests

See the list below:

  • Psychometric evaluation

  • Hearing assessment

Genetic counseling[24]

A negligible risk for Apert syndrome is noted in siblings of affected individuals when parents are not affected, except in the case of germinal mosaicism; in this case, the risk in future siblings depends on the proportion of germ cells that bear the mutant allele.[25]

A 50% risk for Apert syndrome is present in the siblings of an affected individual if a parent is also affected.

A 50% risk for Apert syndrome is observed in offspring of an affected individual.

Advanced paternal age effect in new mutations has been shown clinically and demonstrated conclusively at the molecular level.

Prenatal diagnosis[24]

Despite the striking physical features seen in newborns with Apert syndrome, de novo cases are often not diagnosed prenatally, or are only identified in the third-trimester.[22, 23]

Prenatal ultrasonographic diagnosis can be made based on findings of acrocephaly, mittenlike hands, and proximally placed and radially deviated thumbs.[26] CNS malformations such as mild ventriculomegaly and agenesis of corpus callosum may be visible in some fetuses with Apert syndrome before the pathognomonic skeletal changes are revealed. The abnormal cranial shape and orbital hypertelorism may be absent or very subtle in the second trimester of pregnancy, becoming obvious only in the third trimester. However, Apert syndrome can be accurately suspected in the second trimester by careful ultrasonographic examination of the fetus, including the extremities and skull shape using 3-dimensional ultrasonography.

Use of 3-dimensional ultrasonography to demonstrate the fetal abnormalities (eg, premature closure of the coronal suture; a wide metopic suture; abnormalities of the hands, feet, and face) is particularly useful in parental counseling.[27]

If the molecular defect has been identified in the affected parent, prenatal molecular diagnosis can be achieved by direct DNA testing on fetal DNA obtained from amniocentesis or chronic villus sampling (CVS). In general, linkage analysis can be considered if a mutation has not been detected in the affected parent (although >98% of patients with Apert syndrome tested so far have FGFR2 mutations) and at least 2 affected relatives are available.

The abnormal sonographic findings with a high suspicion of Apert syndrome should be confirmed by detection of a mutation in the FGFR2 gene. Two mutations, S252W C→G and P253R C→G are found in 98% of patients.[28]

Fetoscopy to visualize fetal anomalies comparable to Apert syndrome in a pregnancy at risk is an invasive procedure and is not currently used.

Noninvasive prenatal diagnosis of Apert syndrome using polymerase chain reaction (PCR) and restriction enzyme digestion of cffDNA in maternal plasma has been reported.[29] Au et al have developed a real-time qPCR assay using molecular beacon probes to detect the S252W mutation in the FGFR2 gene, in fetal DNA extracted from plasma of pregnant women at risk for Apert syndrome.[30]

 

Treatment

Medical Care

Medical management of Apert syndrome includes the following:[24]

  • Protection of the cornea

    • Instill lubricating bland ointments in the eyes at bedtime to protect corneas from desiccation

    • Artificial teardrops during the day

  • Upper airway obstruction during the neonatal period

    • Remove excessive nasal secretions

    • Treat upper airway infection

    • Humidification with added oxygen

    • Judicious use of topic nasal decongestants

  • Sleep apnea

    • Polysomography (a sleep recording of multiple physiologic variables), currently the most reliable method for determining the presence of sleep apnea

    • Continuous positive pressure

  • Chronic middle ear effusion associated with bilateral conductive hearing deficit - Antimicrobial therapy

  • Psychological and social challenges confronted by individuals with Apert syndrome

    • Emotional adjustment

    • Body image development

    • Impact of surgery and hospitalization on children with Apert syndrome

Surgical Care

Surgical management of Apert syndrome includes the following:

  • Protection of the cornea: Lateral or medial tarsorrhaphy is performed in severe cases to narrow the palpebral fissure cosmetically and to protect the corneas and the vision.

  • Upper airway obstruction during the neonatal period: This rarely requires orotracheal intubation.

  • Sleep apnea: Tracheostomy is indicated in severely affected children.

  • Chronic middle ear effusion associated with bilateral conductive hearing deficit: Bilateral myringotomy and placement of ventilation tubes are the most effective treatment.

  • Cranial surgery

    • Removes synostotic sutures

    • Reshapes the calvaria

    • Allows more normal cranial development to proceed with respect to shape, volume, and bone quality

    • Relieves increased intracranial pressure

  • Orbital surgery

    • Correction of ocular proptosis

    • Reduction of increased interorbital distance (hypertelorism)

    • Correction of increased interior malrotation

  • Nasal surgery

    • Infants and children: Nasal reconstruction focuses on correction of the excessively obtuse nasofrontal angle, flat nasal dorsum, and ptotic nasal tip.

    • Teenagers and adults: Reduction of the nasal tip bulk is indicated.

  • Midfacial surgery

    • Normalization of midface appearance

    • Expansion of the inferior orbit

    • Volumetric expansion of the nasal and nasopharyngeal airways

    • Establishment of a normal dentoskeletal relationship

  • Mandibular surgery: Mandibular osteotomies are performed to improve dentoskeletal relations for masticatory and aesthetic benefit.

Other surgical approaches

Surgical care involves early release of the coronal suture and fronto-orbital advancement and reshaping to reduce dysmorphic and unwanted skull growth changes. Craniosynostosis requires multistaged operative procedures. A significant cosmetic improvement is possible. Initial surgery is often performed as early as age 3 months.

Facial cosmetic reconstruction for dysmorphisms is indicated.

A new technique of craniofacial disjunction, followed by gradual bone distraction (Ilizarov procedure), has been reported to produce complete correction of exophthalmos and improvement in the functional and aesthetic aspects of the middle third of the face without the need for bone graft in patients aged 6-11 years.

Surgical separation of digits (mitten-glove syndactyly) provides relatively little functional improvement

Shunting procedure reduces intracranial pressure.

For orthodontic treatment, most patients require 2-jaw surgery (bilateral sagittal split osteotomy with mandibular setback and distraction in the maxilla). During the period of distraction, the orthodontist guides the maxilla into final position using bite planes and intermaxillary elastics.

Reconstructive procedures should be correlated with facial growth and development. Although fronto-orbital advancement and posterior vault correction, if necessary, can be accomplished before age 1 year, monobloc advancement and facial bipartition should not be performed until age 6 or 7 years. When performing monobloc and facial bipartition with distraction, it is particularly instructive to pay attention to facial asymmetry and curvature, as facial bending with these procedures allows for amelioration of the flattened face. To correct occlusion, a Le Fort I procedure with or without sagittal split of the mandible may be necessary at the end of facial growth. All of these reconstructive procedures play an important role in enhancing self-confidence and social integration, making the overall psychological outlook good for patients with Apert syndrome.[31]

A study by Goldstein et al comparing complications of midfacial distraction osteogenesis using halo-type versus semiburied devices found a higher rate of operative repositioning in patients with the halo-type distractor, as a result of malposition or transcranial pin migration. However, patients with semiburied distractors experienced a higher rate of major infections.[32]

Consultations

See the list below:

  • Neurosurgeon

  • Plastic surgeon

  • Oromaxillofacial surgeon

  • Craniofacial anesthesiologist

  • Radiologist

  • Otorhinolaryngologist

  • Orthodontist

  • Dentist

  • Orthopedist

  • Ophthalmologist

  • Clinical geneticist

  • Developmental pediatrician

  • Neurologist

  • Psychiatrist

  • Psychologist

  • Audiologist

  • Speech pathologist

  • Physical and occupational therapy specialist

Diet

See the list below:

  • No special diet is required.

Activity

See the list below:

  • No restriction of activity is required.

 

Medication

Medication Summary

See the list below:

  • Medication is not currently a component of care in patients with Apert syndrome. See Treatment.

 

Follow-up

Further Outpatient Care

See the list below:

  • Carefully monitor postoperative complications.

Further Inpatient Care

See the list below:

  • Admit patients with Apert syndrome for surgical intervention.

  • Tracheostomy may be necessary for airway management.

Transfer

See the list below:

  • Transfer may be indicated for further diagnostic evaluation and surgical intervention.

Complications

See the list below:

  • Potential eye or brain injury

  • Wound infections

  • Leakage of cerebrospinal fluid or meningocele formation

  • Increased intracranial pressure and hydrocephalus

  • Airway obstruction, respiratory insufficiency, and sleep apnea

  • Treatment goals focused on preventing avoidable developmental delays (from raised intracranial pressure and sleep apnea) and reducing operative interventions may potentially improve developmental outcomes.[33]

  • A significant proportion of children have obstructive sleep apnea and may develop supraglottic airway obstruction on induction and emergence from anesthesia, due to the midface anatomical abnormalities associated with Apert syndrome.[34]

Prognosis

See the list below:

  • Prognosis largely depends on the age at operation. Craniosynostosis can result in brain compression and mental retardation unless relieved by early craniectomy. Innovations in craniofacial surgery have enabled children with Apert syndrome to achieve their full potential by maximizing their opportunities for intellectual growth, physical competence, and social acceptance; however, early surgical treatment of craniosynostosis may not alter intellectual outcome.

  • Prognosis depends on associated brain malformations. Malformations of the corpus callosum and size of the ventricles appear to play no role in the final intelligence quotient (IQ) score, though malformations of septum pellucidum have a significant effect.

  • Quality of the family environment is another factor involved in intellectual achievement. Only 12.5% of children with Apert syndrome who are institutionalized reach a normal IQ score, compared with 39.3% of children from a healthy family background.

Patient Education

See the list below:

  • National Organization for Rare Disorders, Inc (NORD)

  • 55 Kenosia Avenue

  • PO Box 1968

  • Danbury, CT 06813-1968

  • Phone: 800-999-6673

  • Fax: 203-798-2291

  • email: orphan@rarediseases.org

  • Apert Syndrome Support Group

  • 8708 Kathy

  • St. Louis, MO 63126

  • Phone: 314-965-3356

  • FACES: The National Craniofacial Association

  • PO Box 11082

  • Chattanooga, TN 37401

  • Phone: 800-332-2373 or 423-266-1632

  • email: faces@faces-cranio.org

  • Apert Support and Information Network

  • PO Box 1184

  • Fir Oaks, CA 95628

  • Phone: 916-961-1092

  • email: apernet@ix.netcom.com

  • Apert Web Page

  • PO Box 2571

  • Columbia, SC 29202

  • Phone: 803-732-2372

  • email: catndon@apert.org

  • Children's Craniofacial Association

  • 13140 Coit Road

  • Suite 307

  • Dallas, TX 75240

  • Phone: 800-535-3643