Apert syndrome: an informative long-term dentofacial outcome

Background

Craniosynostosis is a condition that describes the premature fusion of one or more skull sutures. The incidence has been estimated to range from 1:2000 to 1:2500 live births, and although 80% are ‘non-syndromic’, craniosynostosis has been associated with more than 150 syndromes. The most common craniosynostosis syndromes affected by mutations in fibroblast growth factor reception (FGFR) include Pfeiffer, Crouzon, Muenke and Apert.1 Apert syndrome (AS) (OMIM 101200) was first described in 1909 by French physician Eugène Apert who identified individuals with similar facial characteristics alongside syndactyly.2 AS leads to complex functional and structural abnormalities in the face and extremities and requires multidisciplinary management.

AS presents in around 1:60 000 live births. The syndrome usually occurs due to sporadic mutations in FGFR2; however, an autosomal dominant inheritance pattern has also been shown.3 Wilkie and colleagues found that two variants in FGFR2 mutations are involved in the syndrome: S252W and P253R.4 FGFR signalling contributes to the proliferation, migration, differentiation and survival of cells. In AS, the FGFR2 mutation leads to enhanced differentiation of osteoblasts and a gain-of-function in FGF signalling leading to inhibition of growth particularly at the coronal suture interface and compensative growth at other sutures.3

AS is associated with the general features of bicoronal craniosynostosis, exorbitism, midface retrusion and syndactyly of hands and feet. The changes in skull shape can result in raised intracranial pressure creating complications in vision and neurodevelopment. Some individuals also show mild intellectual disability and speech and hearing impairments. Exorbitism can cause corneal abrasions and scarring due to increased eye exposure. Airway compromise causes issues with feeding and sleep apnoea which may require additional surgeries. Cleft palate and conductive hearing loss are often further complications of the syndrome.5

In relation to a patient’s dentition, individuals with AS are known to frequently present with a delayed eruption pattern. Missing teeth and malformations are also common. Due to the altered jaw sizes, often there is a narrowing of the maxillary arch, class III malocclusion and bilateral crossbite, and crowding of both permanent and deciduous dentitions. Manual dexterity is compromised in these individuals, reducing adequate oral hygiene, causing increased caries and periodontal disease risk.5 6

As with other craniofacial anomalies, the rehabilitation of a patient with AS is coordinated and staged within a multidisciplinary team and numerous surgical and non-surgical management with variations and timings of therapeutic interventions set according to individual requirements.5 These patients and their families often experience a range of emotional and psychological issues associated with the abnormalities and its treatment.7 8

Case presentation

A 14-year-old girl with AS presented with a high-steeped forehead, mild hypertelorism and proptosis with antimongoloid slant, mildly hypoplastic infraorbital and malar regions and a depressed nasal bridge (figure 1A). She was experiencing continuous positive airway pressure (CPAP)-dependent obstructive sleep apnoea with reduced nasal airway, particularly on the left side and a narrow nasal aperture. She was in the late mixed dentition with a class II division 1 incisor relationship on a skeletal 2 base with an increased Frankfort Mandibular Angle (FMA) and increased lower face height. There was fair oral hygiene with moderate lower arch crowding and potentially severe upper arch crowding. The upper had a narrow V-shaped arch form; the incisors were proclined and spaced with the first premolars approximating the distal of the lateral incisors. There was a 12 mm overjet, a deep impinging overbite with an accentuated curve of Spee to the lower arch. The molar relationship was full unit class II, and there was a bilateral buccal crossbite and with an upper midline shift to the left. There was deep periodontal pocketing associated with the mesial and distal aspects of the 16 with gingival recession on the buccal (figure 2A).

The orthopantomogram confirmed the presence of unerupted ectopically placed 13, 23, 28 and the unerupted and impacted 37, 38, 47, 48. Significant bone loss was evident distal to the 16. Cephalometric analysis confirmed the skeletal 2 relationship with retrognathic mandible and vertical maxillary excess (table 1). Also evident was the beaten copper appearance to the inner surface of the frontal bone which is indicative of previous raised intracranial pressure (figure 3A,B).

Prior to presenting, the patient had undergone earlier surgery which involved a fronto-orbital advancement and remodelling (FOAR) as an infant and more recently (at age 9) a Le Fort III distraction advancement. Both operations, which are common in AS, were undertaken to improve compromised upper airway, although the earlier operation also addressed her craniocerebral disproportion and ophthalmic concerns due to early cranial vault suture closure. Additional surgery was also undertaken during infancy to address the syndactyly of hands and feet. Prior to the Le Fort III distraction advancement, there was marked midface retrusion, a reverse overjet and ongoing issues of obstructive sleep apnoea despite CPAP treatment (figure 3A). The distractor placement resulted in the loss of developing teeth 18, 17 and 27 and the probable displacement of the developing 28 tooth bud. It also resulted in bone loss associated with the 16 and limited its long-term prognosis. The distraction was further complicated by a differential advancement resulting in a significant maxillary midline shift to the left. Despite the earlier midfacial advancement, she required CPAP and had difficulties with concentration at school.

Outcome and follow-up

A 5.8-year follow-up showed stable correction of the overjet, overbite and dental midlines, although there has been some constriction of the maxillary posterior teeth resulting in a bilateral buccal crossbite. The current posterior occlusion appears stable with no mandibular displacement and retainers were discarded by the patient 2 years previously after the 16 was extracted due to lack of periodontal support. There has been some minor imbrication of the upper left central incisor and lower incisors with slight space distal to the 12, which do not cause the patient any concern. The patient reports an absence of any breathing or masticatory issues and maintains regular dental hygiene visits. She maintains regular employment and is now no longer requiring CPAP and has much improved gingival health.

The case study of this patient illustrates the need for collaboration and interaction between the multidisciplinary team in planning a comprehensive treatment strategy over an extended time frame. Initial surgeries for AS are often ‘crisis’ driven as in this case, where a FOAR surgical procedure was undertaken to address craniocerebral disproportion and ophthalmic concerns due to early cranial vault suture closure. A subsequent Le Fort III distraction advancement was undertaken due to ongoing compromised upper airway and issues associated with obstructive sleep apnoea despite CPAP treatment.

Following the eruption of the permanent dentition, combined orthodontic and orthognathic surgeries are often required to restore dental function and aesthetic appearance to the face. For this case a Le Fort I osteotomy use undertaken to facilitate surgically assisted maxillary expansion and bony recontouring of the pyriform aperture, followed by fixed appliances and a further Le Fort I maxillary impaction with rotation and BSSO advancement.