What is Apert syndrome?

What is Apert Syndrome?

Apert syndrome is a rare congenital genetic disorder characterized by craniosynostosis (premature fusion of cranial sutures), midface hypoplasia, and symmetric syndactyly (fusion) of the hands and feet, caused by specific missense mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. 1, 2

Genetic Basis

• Apert syndrome results almost exclusively from one of two specific point mutations in the FGFR2 gene 2
• The condition follows an autosomal dominant inheritance pattern, though most cases arise from de novo mutations 3
• These mutations lead to abnormal signaling during craniofacial and limb development 4

Cardinal Clinical Features

Craniofacial Manifestations

• Craniosynostosis with early fusion of coronal sutures and cranial base, resulting in a characteristic brachycephalic (short, wide) skull shape 1, 5
• Midface hypoplasia (underdevelopment of the middle third of the face) creating a characteristic facial appearance with prominent eyes 1, 2
• Maxillary transverse and sagittal hypoplasia leading to severe dental crowding 1
• Pseudo-cleft palate and skeletal anterior open bite 1

Limb Abnormalities

• Symmetric syndactyly of hands and feet (fusion of fingers and toes), which is a defining feature distinguishing Apert from other craniosynostosis syndromes 1, 2

Associated Systemic Abnormalities

• Central nervous system malformations occur in approximately 55% of patients, including corpus callosum hypoplasia (27.8%), ventricular enlargement (27.8%), and septum pellucidum hypoplasia (27.8%) 5
• Visceral abnormalities affecting multiple organ systems 2

Ocular and Ophthalmologic Associations

• Apert syndrome is associated with keratoconus and corneal ectasia, particularly in patients with eye rubbing behavior and diminished mental capacity 6
• This association relates to abnormal retinal function and oculodigital stimulation 6

Complications and Clinical Significance

Intracranial Hypertension

• Increased intracranial pressure is frequently observed due to restricted skull growth from premature suture fusion 5
• This can lead to progressive neurological deterioration if untreated 5

Airway Obstruction

• Midface hypoplasia causes velopharyngeal obstruction and upper airway compromise, leading to sleep-disordered breathing 7
• Severe cases may require tracheostomy if not surgically corrected early 7

Diagnosis

• Prenatal diagnosis is possible through advanced imaging techniques (ultrasound showing cranial abnormalities) and molecular genetic testing for FGFR2 mutations 3
• Postnatal diagnosis is typically clinical, based on the characteristic triad of craniosynostosis, midface hypoplasia, and syndactyly 1
• Temporal bone CT imaging is necessary to assess cochlear abnormalities when planning surgical intervention 7

Management Approach

Surgical Interventions

• Early surgical treatment with fronto-orbital advancement aims to increase intracranial volume and minimize effects of intracranial hypertension 5
• Distraction osteogenesis techniques, including Le Fort III osteotomy or monobloc frontofacial advancement, are the primary surgical approaches for correcting midface retrusion and relieving airway obstruction 7
• Early intervention within the first months to years of life may prevent tracheostomy in severe cases with airway compromise 7
• Surgical bone advancement achieves approximately 1 mm per day through progressive device activation 7

Multidisciplinary Care Requirements

• Affected individuals require lifelong management by a multidisciplinary team including craniofacial surgeons, neurosurgeons, otolaryngologists, orthodontists, and psychosocial support specialists 2, 3
• Complete preoperative head and neck examination documenting all craniofacial anomalies is required 7
• Polysomnography is necessary if sleep-disordered breathing is suspected 7

Prognosis and Quality of Life

• No curative treatment exists, but early surgical and orthodontic interventions can significantly improve both function and aesthetics 3
• Quality of life is heavily influenced by psychosocial factors, necessitating comprehensive psychological support for patients and families 3
• Tracheostomy carries 0-3% mortality risk in young patients, making distraction osteogenesis a preferred alternative when feasible 7

Clinical Pitfalls

• The evidence for optimal timing of surgical intervention remains debated: some surgeons avoid distraction osteogenesis in the first months due to complication risk, while others advocate early intervention to prevent tracheostomy 7
• Significant clinical variation exists among patients, even with the same genetic mutation, requiring individualized assessment 4
• Long-term surgical success rates are approximately 60% for maxillomandibular advancement procedures, indicating potential need for revision surgeries 7