Abstract
The reported prevalence of obstructive sleep apnea (OSA) in patients with syndromic craniosynostosis (SCS) varies due to inconsistent definitions of OSA, lack of uniform diagnostic testing, and different mixes of syndromic diagnoses. The purpose of this study was to determine the prevalence of OSA in symptomatic patients with SCS, and to determine whether this differs by phenotypic diagnosis. A retrospective cohort study of children with SCS was conducted. The primary outcome was presence of OSA diagnosed by polysomnography. The prevalence of OSA was calculated and stratified by diagnosis to compare differences in prevalence and severity (mild, moderate, or severe). The prevalence of OSA in symptomatic patients was 74.2%. Patients with Apert syndrome had the highest prevalence (80.6%), followed by Pfeiffer, Crouzon with acanthosis nigricans, and Crouzon syndromes (72.7%, 66.7%, and 64.7%, respectively). Severe OSA was most common in patients with Pfeiffer syndrome (45.5%), while patients with Apert and Crouzon syndromes were more likely to have moderate OSA (29.0% and 23.5%, respectively). Given that 56.4% of patients with SCS are symptomatic and that 74.2% of these symptomatic patients have OSA, it is recommended that a screening level I polysomnography be part of the clinical care for all patients with SCS.
Obstructive sleep apnea (OSA) is common in patients with syndromic craniosynostosis (SCS) due to midfacial hypoplasia with reduction of the nasopharyngeal and oropharyngeal airway space. The prevalence of OSA in children with SCS has been reported to be between 40% and 83%. The wide range in prevalence is due to inconsistent definitions of OSA, lack of uniform diagnostic testing (i.e., polysomnography), and different mixes of syndromic diagnoses with variability in sample size.
The purpose of this study was to determine the prevalence of OSA in patients with fibroblast growth factor receptor (FGFR)-related SCS using polysomnography, and to establish whether there are differences in the prevalence and severity of OSA based on phenotypic diagnosis.
Materials and methods
This was a retrospective review of patients with SCS presenting to a paediatric teaching hospital between 2000 and 2014. Institutional review board approval was obtained for this study. Following approval, the charts of all patients with a diagnosis of FGFR-related SCS (Apert, Crouzon, Crouzon with acanthosis nigricans, or Pfeiffer syndromes) were identified and reviewed. Patients were excluded from the study if they had been followed for less than 1 year or if they had other causes of airway obstruction (e.g., tracheomalacia or laryngomalacia). Patients with Muenke and Saethre–Chotzen syndromes were not included in this study because none of them underwent polysomnography.
The outcome measure was the presence or absence of OSA diagnosed by attended overnight sleep polysomnography. All polysomnography measures were taken prior to operative interventions for OSA (e.g., adenotonsillectomy, midfacial advancement). Patients were referred for polysomnography evaluation if there was a clinical suspicion of OSA (e.g., snoring, restless sleep, behavioural problems, poor school performance, excessive daytime somnolence). Polysomnography criteria for OSA were those defined in the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events.
An obstructive apnea event was scored when airflow dropped at least 90% from baseline with chest and/or abdominal motion through the entire event, the duration of which was a minimum of at least two baseline breaths. An obstructive hypopnea event was scored when airflow dropped at least 50% from baseline, the duration of which was a minimum of at least two baseline breaths. The event must have been accompanied by: (1) a 3% or greater drop in SaO 2 , (2) an arousal, or (3) an awakening.
The apnea–hypopnea index (AHI) was used to score OSA severity. AHI is defined as the total number of apnea and hypopnea events per hour. An AHI above 1.5 was considered to be abnormal. OSA severity was scored as mild (AHI > 1.5/h and <5/h), moderate (AHI 5–10/h), or severe (AHI > 10/h).
The prevalence of OSA was calculated from the total study cohort. Patients were then stratified by diagnosis to compare OSA prevalence and severity among the different phenotypes of FGFR-related SCS. Data were analysed using Microsoft Excel for Mac v. 14.0.0.
Results
Sixty-two of 110 patients (56.4%) with FGFR-related SCS were symptomatic and underwent polysomnography for the evaluation of OSA. Of the 62 symptomatic patients, 24 were female and 38 were male; mean age at evaluation was 7.6 ± 6.5 years. The phenotypic diagnoses included Apert ( n = 31), Crouzon ( n = 17), Crouzon with acanthosis nigricans ( n = 3), and Pfeiffer ( n = 11) syndromes ( Table 1 ).
| Phenotypic diagnosis | Patients who had polysomnography (%) |
|---|---|
| Apert ( n = 52) | 31 (59.6%) |
| Crouzon ( n = 29) | 17 (58.6%) |
| Crouzon with acanthosis nigricans ( n = 5) | 3 (60.0%) |
| Pfeiffer ( n = 24) | 11 (45.8%) |
The prevalence of OSA in symptomatic patients was 74.2%. Patients with Apert syndrome had the highest prevalence (80.6%), followed by Pfeiffer, Crouzon with acanthosis nigricans, and Crouzon syndromes (72.7%, 66.7%, and 64.7%, respectively). One patient with Crouzon syndrome had moderate OSA, a Chiari malformation, and central sleep apnea.
Severe OSA was most prevalent among patients with Pfeiffer and Crouzon with acanthosis nigricans (45.5% and 33.3%, respectively), whereas moderate OSA was most prevalent in patients with Apert and Crouzon syndromes (29.0% and 23.5%, respectively) ( Fig. 1 ).
Results
Sixty-two of 110 patients (56.4%) with FGFR-related SCS were symptomatic and underwent polysomnography for the evaluation of OSA. Of the 62 symptomatic patients, 24 were female and 38 were male; mean age at evaluation was 7.6 ± 6.5 years. The phenotypic diagnoses included Apert ( n = 31), Crouzon ( n = 17), Crouzon with acanthosis nigricans ( n = 3), and Pfeiffer ( n = 11) syndromes ( Table 1 ).
