Obstructive sleep apnoea and the role of tongue reduction surgery in children with Beckwith-Wiedemann syndrome

Summary

Beckwith-Wiedemann syndrome (BWS) is a rare paediatric overgrowth disorder. Associated macroglossia is a feature of many children with BWS and is felt to be a risk factor for obstructive sleep apnoea (OSA). Sleep-disordered breathing is highly variable in this population. The relationship between degree of macroglossia or other genotypic or phenotypic factors and OSA severity has not been established. The natural history of OSA in this population is unknown; a variety of conservative and surgical therapies have been used to treat OSA in children with BWS but none have been studied systematically. Tongue reduction is the mainstay of surgical therapy for macroglossia associated with BWS, but limited data are available regarding its efficacy in treating OSA or its effect on speech and swallowing. More research is needed to better identify which children with BWS are at risk for OSA and the most effective treatment for these patients.

Introduction

Beckwith-Wiedemann syndrome (BWS) is a paediatric overgrowth and cancer predisposition disorder with an incidence of at least 1 in 10,500 live births¹. Clinical features can be variable based on the mosaic nature of the genetic and epigenetic causes of BWS on chromosome 11 as described below, leading to the characterization of the range of features under the broader domain of the ‘11p Overgrowth Spectrum.’ Classic BWS features include macroglossia, omphalocele, macrosomia, hemihypertrophy, distinct facies (ear creases, midface hyperplasia, facial nevus flammeus), hypoglycemia, and embryonal tumours [1]. Even focusing on one feature such as macroglossia, there is a clinical range of presentations (Figure 1). It has also become increasingly apparent that clinical features correlate with the cause of BWS.

BWS is caused by genetic or epigenetic changes on chromosome 11p15 (Figure 2). There are several imprinted genes on chromosome 11p15 that are normally expressed in a parent of origin specific manner and regulated by two imprinting control regions. These genes all control growth and include (H19, insulin-like growth factor 2 (IGF2), and CDKN1C. The most common cause of BWS is loss of methylation at imprinting control region 2, KCNQ1OT1:TSS-DMR 2 (IC2) and these patients are more likely to have macroglossia². The second most common cause of BWS is paternal uniparental isodisomy for part or all of chromosome 11 (pUPD11) and these patients demonstrate the largest spectrum of clinical features and can have macroglossia. Gain of methylation at imprinting control region 1, H19/IGF2:IG-DMR (IC1) and maternally inherited mutations in CDKN1C also cause BWS, but less commonly present with macroglossia [2].