**2.2 Apert syndromes**

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 airway.

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 average 3 years 4 months later [16].

## **2.3 Pfeiffer syndrome**

Characterized by features of craniofacial anomalies from mild to severe condition. It includes turribrachycephaly, midface hypoplasia, exorbitism and the pathognomonic features of broad thumbs and great toes with variable soft tissue syndactyly. Other associated features include hypertelorism, strabismus, downslanting palpebral fissures, class III malocclusion and beaked nasal deformity. Again, the majority of cases involve FGFR-2 mutations, 5% of patients express an FGFR-1 mutation and demonstrate less severe phenotype [17, 18]. It is an autosomal dominant inheritance pattern with the incidence of 1 in 100,000 births. A classification system proposed that patients are categorized into three types based upon clinical findings and severity. Type 1 is the classic Pfeiffer syndrome clinical pattern. Type 2 is more severe and associated with the cloverleaf skull and type 3 Pfeiffer syndrome is the most severely affected. In one institution, a review of 28 patients has been conducted and the Cohen subtypes dissemination is 61% type 1, 25% type 2 and 14% type 3 [19]. All patients have undergone numerous corrective surgery. This study recommends aggressive treatment and monitoring on patients' functional conditions to prevent further damage to the vital organ that leads to permanent loss of function.

Therefore, syndromic craniosynostosis is a condition of multiple associated clinical problems with the same pattern of treatment strategies, expected difficulties and pathologic identifications. Profound knowledge of the disease process, pathognomonic findings and clinical situations of each syndrome is essential. Therefore, multidisciplinary approach in total management of the clinical problems is important and must be detected and treated earlier to improve patient's functional conditions and quality of life.
