Marincak Vrankova Zuzana, Krivanek Jan, Danek Zdenek, Zelinka Jiri, Brysova Alena, Izakovicova Holla Lydie, Hartsfield James K, Borilova Linhartova Petra
Clinic of Stomatology, Institution Shared with St. Anne's University Hospital, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Clinic of Maxillofacial Surgery, Institution Shared with the University Hospital Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Front Pediatr. 2023 Jun 27;11:1117493. doi: 10.3389/fped.2023.1117493. eCollection 2023.
Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) - craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia - have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.
小儿阻塞性睡眠呼吸暂停（POSA）是一种病因复杂的多因素疾病。影响上呼吸道通畅的颅面畸形被认为是POSA发病的危险因素。与睡眠相关呼吸障碍（SRBD）相关的颅面特征——颅缝早闭、下颌后缩和小颌畸形、面中部和上颌发育不全——具有高度遗传性，并且在患有POSA的非综合征儿童中也可能以较轻的形式出现。由于遗传因素在POSA和颅面畸形中均起作用，我们推测一些与特定颅面特征相关且参与口面部区域发育的基因也可能被视为POSA的候选基因。与成人相比，儿童POSA的遗传背景研究较少；到目前为止，仅进行了一项关于POSA的全基因组关联研究；然而，该研究排除了患有颅面疾病的儿童。在这篇叙述性综述中，我们讨论了通常与严重颅面畸形和高发性睡眠相关呼吸障碍（SRBD）（包括POSA）相关的综合征。我们还总结了有关其遗传背景的信息，并据此提出了30个影响颅面发育的POSA候选基因，这些基因可能在患有综合征的儿童中起作用，并确定了其中7个基因，这些基因先前与非综合征儿童中对POSA发病有风险的颅面特征相关。循证方法支持这样的观点，即这些候选基因的变异即使在这些儿童中也可能导致POSA表型，因此，在未来针对普通儿科人群的研究中应予以考虑。
