**2.1 Crouzon syndromes**

*Spina Bifida and Craniosynostosis - New Perspectives and Clinical Applications*

Therefore, corrective surgery in syndromic craniosynostosis were developed in relation to its deformities and functional issues. Conventional craniofacial surgical techniques, such as strip craniectomy, fronto-orbital advancement, and Le Fort III procedures proved to be reliable to treat symptomatic syndromic craniosynostosis. However, limitations were observed in severe conditions where large segmental advancement were required, difficulty to close the gap primarily as well as inadequate stability secondary to soft tissue restriction and unstable bone segment fixation. These limitations thus causing relapse and creating less than an ideal long-term outcome [4]. Hence distraction osteogenesis (DO) were introduced to provide a reliable surgical alternative in achieving superior segmental advancement compared with conventional techniques in treating functional issues in syndromic

Syndromic craniosynostosis patients usually presented with multiple major functional disturbances which requires multi-disciplinary management including maxillofacial surgery, neurosurgery, plastic surgery and ENT among others. As such, the indication for each major surgery in paediatric patients with this condition should be discussed by the craniofacial team members as the procedure carries

Craniosynostosis was first known as craniostenosis that was introduced by German pathologist, Virchow in 1851. It was then changed to craniosynostosis and widely accepted ever since [6]. Craniosynostosis is a condition whereby the process of early or premature fusion of the skull sutures happens that leads to the unwanted growth pattern of the skull. The skull will not be able to grow perpendicular to the fused suture but instead will grow in parallel direction to the fused suture. The brain will use the space available to grow and cause an abnormal head shape and facial features [7]. In cases whereby the skull does not have any spaces due to fused sutures, the brain will continue to grow thus causing increased in intracranial pressure hence patient will develop visual disturbances, sleeping impairment due to airway disruption, eating difficulties because of unusual jaw growth and reduction

Most known craniosynostosis cases are nonsyndromic and can occur as an isolated event or associated with other skeletal and developmental anomalies in specific clinical features for recognized syndromes. Patients who have been diagnosed with syndromic craniosynostosis are much more complex and require a multidisciplinary approach to effectively manage all the problems faced. Most of the syndromic craniosynostosis cases are due to genetic defect that may present as autosomal dominant, autosomal recessive and X-linked patterns of inheritance. The molecular genetic protocol for the diagnosis of syndromic craniosynostosis such Crouzon syndrome includes first-line tests of FGFR2 exons IgIIIa and IgIIIc followed by second-line tests of FGFR2 exons 3, 5, 11, and 14 to 17 and FGFR3 Pro250Arg and Ala391Glu as proposed by Wilkie et al. [7]. There are multiple types of syndromic craniosynostosis cases but almost all of the them shared the same craniomaxillofacial features such as exophthalmos, midface hypoplasia, cranial base anomalies as well as abnormal face with the additional limb anomalies [8–9]. Syndromic craniosynostosis occurs in 1:8750 newborns [10–13]. The most common syndromic craniosynostosis cases identified and managed are Crouzon, Apert, and Pfeiffer syndromes. These syndromes may be presented with identical craniomaxillofacial features. Therefore, it is prudent to differentiate to achieve an accurate

diagnosis by relating to other features such digital or limb anomalies.

**2. Syndromic craniosynostosis and the genetic perspectives**

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craniosynostosis.

in mental development.

substantial mortality and morbidity risks [5].

Clinically, patients may present with brachycephaly, small or shallow orbits with exophthalmos, midface hypoplasia and occlusal anterior open bite. However, there are no recorded cases that anomalies involving limbs are present. It is an autosomal dominant inheritance pattern that showed mutations in the fibroblast growth factor receptor 2 (FGFR-2) and occurred in 1 in 25,000 live births thus the most common syndromic craniosynostosis identified. Patients who have been diagnosed often have normal intelligence. Several cases identified as higher risk of increased intracranial pressure compared to other syndromic craniosynostosis cases [8, 14, 15]. The most common synostosis pattern observed is bicoronal synostosis which leads to brachycephalic shape, others such as scaphocephaly, trigonocephaly and cloverleaf skull have been diagnosed. Early fusion of cranial sutures resulted in shallow orbits and eye proptosis, small & high arched palate and anterior open bite. Eye proptosis or exorbitism can cause exposure conjunctivitis, keratitis, visual acuity problems and herniation of the globe. The synostosis will lead to midface hypoplasia as well and with normal development of mandible, class III skeletal profile & malocclusion formed. There are also other conditions reported such conductive hearing deficit, strabismus and hydrocephalus.
