1. Craniosynostosis: a case of Apert Syndrome
Victoria Schunemann, MS4

2. The Case 6 yo Romanian female with: PSurgHx FamHx Physical Exam
Apert syndrome
ADD
Speech delay
PSurgHx
R syndactyly release
“Hip” surgery
FamHx
No Apert syndrome or non-syndromic craniosynostosis
Physical Exam
HEENT: turribrachycephaly; hypertelorism; proptosis; midface retrusion; relative prognathia
Ext: previously repaired syndactyly on R, fused fingers on L; b/l fused toes
Neuro: PERRL, EOMI, CN II-XII intact; moves all extremities equally with good strength

3. The Case
*NOT actual patient*

4. The Case

5. The Case
Xray

6. The Case
Xray

7. The Case CT

8. The Case CT

9. The Case CT

10. The Case CT

11. The Case CT

12. Apert Syndrome 1894 – Wheaton 1906 – Apert Triad Other findings
Craniosynostosis
Bilateral coronal sutures
Midface hypoplasia
Symmetric syndactyly
hands AND feet
Other findings
Megalencephaly
Hypoplasia of corpus callosum
Aplasia of septum pellucidum
Developmental delay
Fusion of other joints
Including cervical spine

13. Apert Syndrome Anomalies CNS Orbits Midface Hydrocephalus
Distorted ventricles
Chiari malformations
Orbits
Proptosis
Hypertelorism
Strabismus
Amblyopia
Midface
Impaired respiration
Obstructive sleep apnea
Virchow

14. Apert Syndrome Epidemiology
4.5% of cases of syndromic craniosynostoses
Incidence
1 in 160,000 births
Prevalence
1 in 55,000 births
M~F
Asian; Hispanic

15. Apert Syndrome Cranial development Matrix theory
Base – endochondral ossification
Calvaria – intramembranous ossification

16. Apert Syndrome Genetics Autosomal dominant Majority de novo mutations
85% vs. 15%
Risks
Advanced paternal age
FGFR2
2 missense mutations
755C->G, resulting in Ser252Trp
758C->G, resulting in Pro253Arg

17. Apert Syndrome FGFR Functions Tyrosine kinase receptor
Embyronic development
mesoderm induction
antero-posterior patterning
limb development
ossification
neural induction
neural development
Mature tissue
angiogenesis
keratinocyte organization
wound healing processes

18. Apert Syndrome Molecular Biology Gain of Function
Increased affinity for ligands
Loss of ligand binding specificity
Epithelial – mesenchymal interaction

19. Treatment Combined craniofacial case with plastics
Monobloc with distraction and cranial vault remodeling

20. Treatment
Bicoronal sinusoidal incision

21. Treatment Flap raised with exposure to orbits and zygomatic arches
Pericranium dissected off cranium for flap
Bi-frontal craniotomy
Recontouring of frontal bone with barrel staves and burring
Dissection down to foramen cecum

22. Treatment Gingival incisions
Osteotomies – zygomatic arches, sphenoids, orbits, posterior nose, lateral pterygoid plates
Free midface from cranium
Disimpaction forceps to mobilize face

23. Treatment
Distractor placement and mobilization to 15 mm before returning to 3mm
Frontal bone plated to supraorbital bar

24. Apert Syndrome Summary Triad Mutations in FGFR2 Treatment
Craniosynostosis of coronal sutures
Bilateral syndactyly of fingers and toes
Midface hypoplasia
Mutations in FGFR2
Majority de novo
Can be familial
Gain of function
Treatment
Surgery at early age
Can require continued surgeries
Family support

25. Post-Op

26. Thanks to… UCSD Neurosurgery Rady Children’s Hospital Dr. Meltzer
Dr. Cohen

27. Works Cited
Agochukwu NB, Solomon BD, et al. Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses. Childs Nerv Syst Sep;28(9); Epub 2012 Aug 8. Bruce DA.Consensus: Craniofacial synostoseS: Apert and Crouzon syndromes. Child's Nerv Syst (1996) 12: Carinci F, Pezzetti F, Locci P, et al. Apert and Crouzon syndromes: clinical findings, genes and extracellular matrix. J Craniofac Surg May;16(3): Cunningham ML, Seto ML, et al. Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofacial Res 10, 2007; 67–81. Goodrich J. (2008). Craniofacial Syndromes, In B. Brandenburg & I Ip (Eds.), Principles and Practice of Pediatric Neurosurgery ( ). New York: Theeme Medical Publishers, Inc. Ibrahimi OA, Chiu ES, et al. Understanding the molecular basis of Apert syndrome. Plast Reconstr Surg Jan;115(1): Katzen JT, McCarthy JG. Syndromes involving craniosynostosis and midface hypoplasia. Otolaryngol Clin North Am Dec;33(6): , vi. Kimonis V, Gold J, et al. Genetics of Craniosynostosis. Semin Pediatr Neurol 14: Morriss-Kay GM, Wilkie AOM. Growth of the normal skull vault and its alteration in craniosynostosis: insights from human genetics and experimental studies. J. Anat. (2005) 207, pp637–653.. Ocal E, Sun P, Persing J. (2008). Craniosynostosis, In B. Brandenburg & I Ip (Eds.), Principles and Practice of Pediatric Neurosurgery ( ). New York: Theeme Medical Publishers, Inc. Rice DP (ed): Craniofacial Sutures, Development, Disease and Treatment. Front Oral Biol. Basel, Karger, 2008, vol 12, p