Clinical reviewCraniofacial syndromes and sleep-related breathing disorders
Introduction
Sleep disordered breathing (SDB) encompasses obstructive sleep apnea (OSA), central sleep apnea and nocturnal hypoventilation. Of these, OSA is by far the most commonly described in children with craniofacial syndromes and thus, the main focus of this review. OSA is characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction that disrupts both normal ventilation during sleep and normal neurophysiological sleep patterns [1]. The reported prevalence in children with craniofacial syndromes ranges from 7 to 67% depending on the stringency of the diagnostic criteria and population studied [2]. OSA can result in a wide array of morbidities, including cardiovascular, metabolic, neurocognitive and behavioral sequelae, significantly impacting on quality of life [3], [4], [5], [6].
To illustrate the typical presentation and clinical course of SDB in children with craniofacial syndromes, we will start by describing the case of a child with Crouzon syndrome with severe OSA, and use this to illustrate the common management problems encountered in these complex patients. As it is not possible in a targeted review to cover all genetically derived craniofacial syndromes, we have concentrated on the first two categories in the Whitaker classification of craniofacial anomalies: I) clefts and II) synostoses [7]. We discuss the unique aspects of each condition with respect to SDB, and highlight the current treatment strategies. Some of the treatment modalities are common to those used in otherwise healthy children with OSA, namely, adenotonsillectomy, continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) and in the refractory cases, tracheostomy. However, there are some distinct approaches to the management of children with craniofacial syndromes, such as insertion of nasopharyngeal airway (NPA) and surgical interventions such as midface advancement and mandibular distraction osteogenesis that will be included in the text and described in more detail.
Section snippets
Case study
AB was born at 34 weeks gestation. He had respiratory distress at birth, and needed admission to the neonatal intensive care unit where he received CPAP for 5 days. He was initially prevented from any oral intake, and therefore on intravenous fluids. When his respiratory distress improved, nasogastric feeding was attempted, but not even the smallest nasogastric tube could be passed through his nose. An orogastric tube was passed instead, and he was evaluated by an otolaryngologist.
Craniosynostoses
Craniosynostosis affects an estimated 1 in 2500 births. It occurs as part of a syndrome in approximately 40% of all cases, and the common feature is the premature fusion of one or more of the skull sutures. The more common syndromes include Pfeiffer, Apert, Crouzon, Muenke, Saethre-Chotzen and Carpenter syndromes. Mutations in the fibroblast growth factor receptor (FGFR) genes are responsible for most of the craniosynostoses [8]. Pfeiffer syndrome is associated with mutations in the FGFR1 gene;
Cleft lip/palate (CL/P)
Embryonic development of the primary palate (lip and alveolus) and secondary palate (soft and hard palate) occurs between weeks 6–9 of gestation. Cleft lip/palate (CL/P) results when the medial nasal process fails to contact or maintain contact with the lateral nasal and maxillary processes [42]. CL/P has an incidence of approximately 1 per 1000 births, although there is substantial geographical and ethnic variation [43]. An epidemiological study showed that 70% of the cases were isolated CL/P,
Treatment/adenotonsillectomy
Adenotonsillectomy is currently the first line treatment recommended for otherwise healthy children with OSA who have adenotonsillar hypertrophy. However, adenoidectomy can result in velo-pharyngeal insufficiency in children with CL/P [73], [74]. Most surgeons therefore advocate and opt to perform partial adenoidectomy to minimize the risk of this complication. Finkelstein et al. described their experience of performing transnasal endoscopic partial adenoidectomy in 10 patients with submucous
Pierre Robin sequence
The triad of micrognathia, glossoptosis and resultant airway obstruction was described by Pierre Robin in 1923, who identified “a fall of the base of the tongue as a new cause of nasopharyngeal respiratory impairment” [78]. It is commonly associated with a cleft palate: the widely accepted paradigm is that mandibular hypoplasia results in displacement of the tongue superiorly and posteriorly between the palatal shelves, thus preventing their fusion in weeks 8–10 of gestation. This aberrant
Treacher–Collins syndrome
Treacher-Collins syndrome (TCS) is an autosomal-dominant disorder of craniofacial development, with an estimated incidence of 1 in every 50,000 live births. It is characterized by hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, conductive hearing loss, downward slanting palpebral fissures, colobomas of the lower eyelids and pharyngeal hypoplasia [123] (Fig. 5). The majority of patients are heterozygous for a mutation in
Future work and unanswered questions
Most of the published literature on craniofacial abnormalities and sleep is limited by including either individual case reports or retrospective reviews that encompass relatively small patient numbers. Conclusions from such studies and reports are further hampered by the lack of objective data such as PSG findings pre and post intervention, the small number of studies that have looked at long-term outcomes, and the heterogeneous phenotype of these patients, which dilutes the already scarce
Conclusion
The diagnosis of sleep disordered breathing should be considered in all children with craniofacial syndromes. The most common sleep disorder is OSA, though central apneas during sleep have also been reported, particularly in the craniosynostoses. The etiology of the OSA is multifactorial, and includes anatomical facial and upper airway factors such as midface hypoplasia and glossoptosis, as well as factors resulting in increased upper airway collapsibility such as oropharyngeal dysfunction.
Funding sources
LKG and DG are supported by National Institutes of Health grants HL-65270.
Conflict of interest
The authors have no conflict of interest or outside funding sources to disclose.
Acknowledgments
We would like to acknowledge Dr. P. Ayliffe, Oral and Maxillofacial surgeon at Great Ormond Street Hospital for providing some of the photos and for his feedback on the manuscript.
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