CRANIOSYNOSTOSIS: A
CASE OF APERT
SYNDROME
Victoria
Schunemann,
MS4
THE CASE
 6 yo Romanian female with:
 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
THE CASE
 *NOT actual patient*
THE CASE
THE CASE
 Xray
THE CASE
 Xray
THE CASE
 CT
THE CASE
 CT
THE CASE
 CT
THE CASE
 CT
THE CASE
 CT
APERT SYNDROME
 1894 – Wheaton
 1906 – Apert
 Triad
 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
APERT SYNDROME
 Anomalies
 CNS
 Hydrocephalus
 Distorted ventricles
 Chiari malformations
 Orbits




Proptosis
Hypertelorism
Strabismus
Amblyopia
 Midface
 Impaired respiration
 Obstructive sleep apnea
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
APERT SYNDROME
 Cranial development
 Matrix theory
 Base – endochondral ossification
 Calvaria – intramembranous ossification
http://wps.aw.com/bc_marieb_happlace_7_oa/42/10965/2807221.cw/index.html
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
APERT SYNDROME
 FGFR
 Tyrosine kinase receptor
 Functions
 Embyronic development






mesoderm induction
antero-posterior patterning
limb development
ossification
neural induction
neural development
 Mature tissue
 angiogenesis
 keratinocyte organization
 wound healing processes
https://www.qiagen.com/geneglobe/pathwayview.aspx?pathwayID=180
APERT SYNDROME
 Molecular Biology
 Gain of Function
 Increased affinity for ligands
 Loss of ligand binding specificity
 Epithelial – mesenchymal interaction
TREATMENT
 Combined craniofacial case with plastics
 Monobloc with distraction and cranial vault remodeling
TREATMENT
 Bicoronal sinusoidal incision
TREATMENT
 Flap raised with exposure to orbits and zygomatic arches
 Pericranium dissected of f cranium for flap
 Bi-frontal craniotomy
 Recontouring of frontal bone with barrel staves and burring
 Dissection down to foramen cecum
TREATMENT
 Gingival incisions
 Osteotomies – zygomatic arches, sphenoids, orbits, posterior
nose, lateral pterygoid plates
 Free midface from cranium
 Disimpaction forceps to mobilize face
TREATMENT
 Distractor placement and mobilization to 15 mm before
returning to 3mm
 Frontal bone plated to supraorbital bar
APERT SYNDROME
 Summary
 Triad
 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
POST-OP
THANKS TO…




UCSD Neurosurgery
Rady Children’s Hospital
Dr. Meltzer
Dr. Cohen
WORKS CITED
Agochukwu NB, Solomon BD, et al. Impact of genetics on the diagnosis and clinical management of syndromic
craniosynostoses. Childs Nerv Syst. 2012 Sep;28(9);1447-63. Epub 2012 Aug 8.
Bruce DA.Consensus: Craniofacial synostoseS: Apert and Crouzon syndromes. Child's Nerv Syst (1996) 12:734736.
Carinci F, Pezzetti F, Locci P, et al. Apert and Crouzon syndromes: clinical findings, genes and extracellular
matrix. J Craniofac Surg. 2005 May;16(3):361-8.
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 (289-309). New York: Theeme Medical Publishers, Inc.
Ibrahimi OA, Chiu ES, et al. Understanding the molecular basis of Apert syndrome. Plast Reconstr Surg. 2005
Jan;115(1):264-70
Katzen JT, McCarthy JG. Syndromes involving craniosynostosis and midface hypoplasia. Otolaryngol Clin North
Am. 2000 Dec;33(6):1257-84, vi.
Kimonis V, Gold J, et al. Genetics of Craniosynostosis. Semin Pediatr Neurol 14:150-161.
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 (265-288). New York: Theeme Medical Publishers, Inc.
Rice DP (ed): Craniofacial Sutures, Development, Disease and Treatment. Front Oral Biol. Basel, Karger, 2008,
vol 12, p 91-106