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

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 in mental development.

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.

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average 3 years 4 months later [16].

**2.3 Pfeiffer syndrome**

airway.

*Craniofacial Corrective Surgery in Syndromic Craniosynostosis*

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

Often patients will present with turribrachycephaly, midface hypoplasia, symmetrical syndactyly of both hands and feet. It is also an autosomal dominant inheritance pattern with mutations in FGFR-2 occurring in 1 in 100,000 births with cases seen are sporadic new mutations. Bicoronal synostosis with large anterior fontanelle, bitemporal widening and occipital flattening is common presentation in most patients. In this syndrome, the midface hypoplasia is more severe than others with concavity of the face, very shallow orbits, mild hypertelorism and downslanting palpebral fissure, eye proptosis, cleft palate, anterior open bite. It will have the characteristic depressed nasal bridge and downward tip resulting in parrot beak deformity. The severe hypoplastic midface in Class III skeletal features will result in a small airway that causes airway compromise needing a tracheostomy to secure the

Pathognomonic syndrome will be the hand syndactyly which often involve fusion of the second, third and fourth fingers that lead to middigital hand mass with the first and fifth fingers may also join. In certain cases, if the thumb is free, it is broad and deviates radially. In the feet, syndactyly will involve the second, third and fourth toes. Patients will suffer loss of function and referral to a hand surgeon is essential. Many patients have normal intelligence despite of some cases delayed mental development identified. Marruci et al. published the Great Ormond Street Hospital data on the expectant management of their patients in raised ICP in Apert syndrome. Their protocol is to offer cranial vault expansion only in the setting of confirmed elevation of ICP. Raised ICP developed in 83% of patients, 50% in the first year of life with the average age at onset was at 18 months. 35% of those treated successfully for their first episode however, went on to develop a second episode on

Characterized by features of craniofacial anomalies from mild to severe condition. It includes turribrachycephaly, midface hypoplasia, exorbitism and

*DOI: http://dx.doi.org/10.5772/intechopen.94584*

**2.1 Crouzon syndromes**

and hydrocephalus.

**2.2 Apert syndromes**
