CRANIOSYNOSTOSIS: A Victoria

CASE OF APERT Schunemann,

MS4
SYNDROME
 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
mesoderminduction
antero-posterior patterning
limb development
ossification
neural induction
neural development
Mature tissue
angiogenesis
keratinocyte organization
wound healingprocesses
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 off 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 Childrens 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) 12:734-
736.
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; 6781.
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, pp637653..
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