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2008-07-29-11 Apert syndrome © Suchet
Apert syndrome


Ian Suchet, MD.




Apert syndrome accounts for 4.5% of all patients with craniosynostotic syndromes [1]. It is classically characterized by the triad of coronal craniosynostosis, midfacial hypoplasia and symmetric bony syndactyly of the hands and feet [2].

The prevalence of Apert syndrome has been estimated at 15 cases per million live births [3]. Despite being inherited as an autosomal dominant disorder, the vast majority of cases (>98%) are sporadic, as a result of a de novo mutation in the sperm. The incidence of such mutations increase exponentially with paternal age [1].

Apert syndrome has frequently been diagnosed early in pregnancy in at risk patients using various methods such as fetoscopy, fetal ultrasound and molecular testing. The high incidence of sporadic cases makes diagnosis a challenge [2]. Occasionally several sonograms are required to confirm the diagnosis if the specific features are not recognized. Various non specific suspicious sonogram findings have been reported in the literature (Table 1), many of which lead to a more detailed exam that detects the specific triad of features.

Even though the ultrasound features may be specific enough the make the diagnosis of Apert syndrome, confirmation may be performed with molecular testing. Known mutations that cause the syndrome (found in 98-99% of cases) are two recurrent missense mutations of the fibroblast growth factor receptor 2 gene (FGFR2) involving two adjacent amino acids (S252W and P253R) [4].

Although patients of normal intelligence have been found, approximately one half of affected individuals presents with varying degrees of mental retardation [5]. Majority of individuals will require multiple surgeries to correct their syndactyly. In addition, surgeries may be performed to increase intracranial volume to improve neurological outcome or for cosmetic reasons [2,6].

Ultrasonographic features

All newborns with Apert Syndrome have coronal synostosis [10]. This abnormality has been identified as early as 19 weeks gestation [4] however in many cases cannot be seen until the third trimester. Demonstration of the premature fusion of the coronal suture helps in differentiating Apert syndrome from other forms of craniosynostosis. Commonly lambdoid and sagittal craniosynostosis have also been described. Such fusion results in common skull shape abnormalities (Table 2) such as frontal bossing [20]. It has been found that in most cases of Apert syndrome there is a widely patent midline calvarial defect extending from the glabella to the posterior fontanelle (metopic suture) [10,11,20]. Ocular hypertelorism and proptosis are important associated features that raise the possibility of Apert syndrome [1].

Midface hypoplasia is classically characterized in Apert syndrome which may result in a markedly depressed nasal bridge, appearing short and wide with a bulbous tip [21]. Many observations have been made about abnormal ear morphology in Apert syndrome. In a study by Farkas [22], low set ears, and a tendency to disproportion, with widening and small inclination of the longitudinal axis were demonstrated in all subjects.

• Skull:
o Oxycephaly and flattened occiput.
o Hypertelorism and bilateral exophthalmos.
o Underdeveloped maxilla and prognathism (mid-facial hypoplasia), choanal atresia.
o Cervical spine may be fused.

• Hands and Feet:
o Fusion of distal portions of phalanges, metacarpals and carpals of 2nd, 3rd and 4th digit (Syndactyly).
o Absence of middle phalanges.
o Missing / supernumerary carpal / tarsal bones.
o Pseudoarthrosis.
o Broad distal thumb and big toes.

The detection of bilateral Syndactyly should raise the suspicion of Apert syndrome. Syndactyly of the 1st or 2nd through 5th fingers, known as “mitten hands” separate Apert syndrome from the other forms of craniosynostosis [2]. This feature is seen in approximately 97% of syndromes [12].

Table 1. Non specific suspicious ultrasound findings in Apert syndrome.


  • Brain/CNS                                                                       
    • Ventriculomegaly (48.5%) [4]
    • Agenesis of the Corpus Callosum [1]
    • Holoprosencephaly [1]
    • Partial absence of Septum Pellucidum, Hydrocephalus (9%) [15]
    • Gyral Abnormalities, Posterior Fossa Anomalies. [4]
    • Megalencephaly [16]
    • Thickened Nuchal Fold [17]
    • Thickened Nuchal Translucency [2]
  • Craniofacial 
    • Choanal Stenosis (14%) [4]
    • Cleft Soft Palate [4]
    • Ectopia Lentis [21]
    • Frontal Bossing, Depressed Nasal Bridge [10]
    • Proptosis [2]
    • Low set ears [22]
  • Cardiac
    • Cardiovascular Abnormalities [18]
    • Hypoplastic Left Heart [2]
  • Genitourinary (10%)
    • Hydronephrosis [2]
    • Polycystic Kidney [4]
  • Gastrointestinal (1.5%) [14]
    • Diaphragmatic Hernia [2]
    • Pyloric Stenosis, Esophageal Atresia [18]
  • Obstetrical
    • Polyhydramnios [19]
  • Skeletal
    • Reduced Foot Length with Abnormal Toes [4]
    • Broad First Toe [2]


Antenatal 3D Ultrasound

CT autopsy bone algorithm

CT autopsy soft tissue algorithm

Pathological specimen

- Hypertelorism
- Proptosis
- Wide metopic suture

Facial profile – soft tissues
- Facial profile – soft tissues
- Frontal bossing
- Depressed nasal bridge
- Low set ears
- Orbital proptosis

Frontal profile – bone
- Synostosis coronal suture
- Frontal bossing
- Orbital proptosis

- Soft tissue and osseous syndactyly
- “mitten” hand

- Soft tissue and osseous syndactyly


  • Type I - Apert syndrome (acrocephalosyndactyly).

  • Type II - Vogt cephalosyndactyly.

  • Type III - Acrocephalosyndactyly with asymmetrical skull and mild syndactyly.

  • Type IV - Wardenburg type.

  • Type V - Pfeiffer type.


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2. Skidmore DL, Pai AP, Toi A, et al. Prenatal diagnosis of Apert syndrome: report of two cases. Prenat Diagn 2003;23: 1009-1013.
3. Cohen MM Jr, Kreiborg S, LAmmer EJ, et al. Birth prevalence study of the Apert aynsrome. Am J Med Genet. 1992; 42; 655-659.
4. Ferreira JC, Carter SM, Bernstein PS, et. al. Second-trimester molecular prenatal diagnos of sporadic Apert syndrome following suspicious ultrasound findings. Ultrasound Obstet Gynecol 1999; 14:426-430.
5. Esser T, Rogalla P, Bamberg C, Kalache K, Application of the three-dimensional maximum mode in prenatal diagnosis of Apert syndrome. Am J of Obstetric and Gynecology 2005;193:1743-1745.
6. Renier D, Arnaud E, Cinalli G, et al. Prognosis for mental function in Apert;s syndrome. J Neurosurg 1996; 85:66-72.
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9. Taylor AM, Jones R, Offiah A, et al. Postmortem magnetic resonance imaging as an adjunct to the diagnosis of skeletal dyslplasias: short-rib polydactyly syndrome. Ultrasound Obstet Gynecol 2006; 27; 585-586.
10. Faro C, Chaoui R, Webrzyn P, et al. Metopic suture in fetuses with Apert syndrome at 22-27 weeks of gestation. Ultrasound Obstet Gynecol 2006; 27:28-33.
11. Lam H, Lo T, Lau E, Chin R, Tang L. The Use of 2 and 3- Dimensional Sonographic Scans in the Evaluation of Cranial Sutures. J Ultrasound Med 2006; 25:1481-1484.
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13. Gordijn SJ, Erwich JJ, Khong TY. Value of the perinatal autopsy; critique. Pediatr Dev Pathol 2002; 5; 480-488.
14. Boyd PA, Tondi F, Hicks NR, Chamberlain PF. Autopsy after termination of pregnancy for fetal anomaly: retrospective cohort study. BMJ 2004; 328;137.
15. Renier D, Arnaud E, Cinalli G, Sebag G, Zerah M, Marchac D. Prognosis for mental function in Aperts syndrome. Neurosurg 1996; 85:66-72.
16. Gosain AK, McCarthy JG, GLatt P, et. al. A study of intracranial volume in Apert syndrome. Plast Reconstr Surg. 1995;95;284-295.
17. Chenoweth-Mitchell C, Cohen GR. Prenatal sonographic findings of Apert syndrome. J Clin Ultrasound 1994;22: 510-514.
18. Cohen MM, Kreiborg S. Visceral anomalies in the Apert syndrome. Am J Med Genet 1993; 45:758-760.
19. Hill BD, Thomas RJ, Peterson CS. The ultrasound detection of Apert syndrome. J Ultrasound Med. 1987;6:601-604.
20. Cohen MM, Kreiborg S. A clinical study of the craniofacial features in Apert syndrome. Int. J. Oral Maxillofac. Surg. 1995;25; 45-53.
21. Chen H. E medicine: Apert Syndrome. 2005., [Accessed January 2006].
22. Farkas L.G. Ear morphology in Treacher Collins’, Apert’s and Crouzon’s syndromes. Arch Otorhi.


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