Prevalence:

• 1 in 2,000 births.
• Associated with advanced paternal age.

Ultrasound diagnosis:

• Premature fusion of cranial sutures resulting in abnormal shapes of the cranium.

Associated abnormalities:

• In 90% of cases, craniosynostosis is an isolated finding.
• In 10% of cases, there is an association with any one of 150 syndromes, including, Crouzon syndrome, Muenke syndrome, Saethre-Chotzen syndome, Apert syndrome, Pfeiffer syndrome

Investigations:

• Detailed ultrasound examination. Special attention should be paid to fetal hands, midface, heart and central nervous system.
• Fetal MRI provides useful information.
• Detailed family history and consultation with geneticist: if the family history is negative for isolated craniosynostoses, prenatal karyotyping to rule out chromosomal abnormalities is recommended.
• Craniosynostosis is caused by mutations in the FGFR-2, FGFR-3, TWIST, and EFNB-1 genes.

Follow up:

• Follow-up should be standard.

Delivery:

• Standard obstetric care and delivery in tertiary center,

Prognosis:

• Newborns might have difficulties with breathing, feeding and vision.
• Increased intracranial pressure, which is present in one third of the newborns, might affect intelligence and neurodevelopment. Optimal timing for surgical repair should be planned.

Recurrence:

• De novo mutations: no increased risk of recurrence.
• Syndromic forms with positive family history: 25% and 50% risk of recurrence depending on the associated syndrome.

Crouzon syndrome

Prevalence:

• 1 in 25,000 births.

Ultrasound diagnosis:

• Variable craniosynostosis (most often bicoronal), midface hypoplasia with “beaked” nasal tip, mandibular prognathism, and exorbitism (protrusion of the eyeballs as a result of shallow orbits).
• Normal hands and feet.

Investigations:

• Autosomal dominant inheritance of mutation in the FGFR2 gene. The diagnosis can be made by invasive testing.

Prognosis:

• Most affected individuals are of normal intelligence.
• Bulging eyes and vision problems.

Muenke syndrome

Prevalence:

• 1 in 30,000 births.

Ultrasound diagnosis:

• Coronal craniosynostosis.
• Mild abnormalities of the hands and feet, including carpal and tarsal fusion, brachydactyly, thimble-like middle phalanges and cone-shaped epiphyses.

Investigations:

• Autosomal dominant inheritance of mutation in the FGFR3 gene. The diagnosis can be made by invasive testing.

Prognosis:

• Most affected individuals are of normal intelligence, but some have delayed development and learning difficulties.

Saethre-Chotzen syndrome

Prevalence:

• 1 in 40,000 births.

Ultrasound diagnosis:

• Uni- or bicoronal craniosynostosis, facial asymmetry, deviation of the nasal septum, a low frontal hairline, and small, low set, and posteriorly rotated ears.
• Brachydactyly and partial cutaneous syndactyly of the toes.

Investigations:

• Autosomal dominant inheritance of mutation in the TWIST1 gene. The diagnosis can be made by invasive testing.

Prognosis:

• Most affected individuals are of normal intelligence, but some have delayed development and learning difficulties.

Apert syndrome

Prevalence:

• 1 in 70,000 births.

Ultrasound diagnosis:

• Bicoronal craniosynostosis resulting in brachycephaly, ‘towering skull deformity’, hypertelorism, frontal bossing.
• Brachysyndactyly of hands and feet.
• Other abnormalities: ventricular septal defect, fusion of cervical vertebrae, agenesis of corpus callosum, hydronephrosis and cryptorchidism.

Investigations:

• Autosomal dominant inheritance of mutation in the FGFR2 gene. The diagnosis can be made by invasive testing.

Prognosis:

• 50% chance of mental retardation.
• Need for surgery for synostosis and syndactyly.

Pfeiffer syndrome

Prevalence:

• 1 in 70,000 births.

Ultrasound diagnosis:

• Multisutural craniosynostosis (cloverleaf-shaped skull) and midface hypoplasia with associated hypertelorism and exorbitism.
• Broad, radially deviated thumbs, broad great toes,

Investigations:

• Autosomal dominant inheritance of mutation in the FGFR1 and FGFR2 genes. The diagnosis can be made by invasive testing.

Prognosis:

• Type I: favourable prognosis, normal intelligence.
• Type II: poor neurologic prognosis.