Topics: Apert syndrome, Craniosynostosis, Skull Pages: 14 (1578 words) Published: December 16, 2012
Genetic background of craniosynostosis

• Major malformation present at birth incidence 1: 2100 (3000) • The sutures in the skull close too early (premature fusion) • This results in characteristic head shapes

C a io y o t s s r n s nsoe
P im r r ay Sc n a y eodr c a io y o t s s c a io y o t s s r n snsoe r n snsoe Single suture Isolated event Several sutures One feature of a syndrom

Primary (nonsyndromic) craniosynostoses

Metopic synostosis Coronal synostosis

Sagital synostosis

Lambdoidal synostosis

Sagital synostoses
• Most common (58% of all cases) • Premature closing of sagital suture produces dolihocephaly (doliho = long) scaphocephaly (scapho=boat) • Also called turricephaly (tower-headed), oxycephaly, acrocephaly, hypsicephaly

Sagital synostosis


Sagital synostoses
• Mostly sporadic (72% of all cases) • Family cases (28%) A-D; penetrance ~38% • Male female ratio 3,5 : 1

Dolihocephalia (Scaphocephalia)

Coronal synostoses
• 12-29% of all craniosynostoses • Premature closing of coronal suture produces brachycephaly (short head) • Condition cerrelates with advanced maternal age

Coronal synostosis

• Mostly sporadic (61% of all cases) • Family cases (39%) A-D; penetrance ~60% • Male female ratio 2: 1

Coronal synostoses


Metopic synostoses
• 4-10 % of all craniosynostoses • Premature closing of metopic suture produces trigonocephaly (triangle -shaped head) • Sometimes forehead looks pointed with hypotelorim

Metopic synostosis




Unilateral coronal synostoses
• Premature closing of unilateral coronal suture produces frontal plagiocephaly(asymetrical head shapes)

• Flattening of the forehead on the affected side

Unilateral coronal synostosis



Symptoms of craniosynostosis
• • • • • • • • Sleepiness (or less alert than usual) Scalp veins may be very noticeable Increased irritabitlity High-pitched cry Poor feeding Projectile vomiting Increased head circumference Bulging eyes

Oral defects in craniosynostosis
Clefts •Hypodontia •Hyperdontia •Delayed teeth eruption •Taurodontism •Microdontia •Dens invaginatus •Dentin dysplasia

Dens in dente

Genetic bases
Fibroblast growth factor receptor genes (FGFR genes)

FGFR genes (1-3 involved in craniosynostosis

FGFR involved in craniosynostosis


FGFR 1 gene


FGFR 3 gene

FGFR protein structure

Ig – imunoglobulin TM – transmembrane TK – tyrosine kinase

*HSPGs – heparan sulfate containing proteoglycans

A model of heparin-induced dimerization and activation of the FGF receptors

Bones of the face

Neural crest cells

Normal functions of FGFR
•Cell division •Regulation of the cell growth •Formation of the blood vessels •Wound healing

The expression patterns of FGFR 1-3
Prior ossification FGFR 1 – mesenchyme FGFR 2 – epidermis and mesenchymal condensations FGFR 3 - epidermis, mesenchyme ( levels) During ossification FGFR 1-3 -in the mesenchyme around the mineralized bone (FGFR 3 ) -at 18 week in the periphery of ossification...
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