International Journal of Pediatric Otorhinolaryngology 78 (2014) 1548–1550

Case report

Otolaryngological presentations of Cornelia de Lange syndrome

Jane Hamilton a, W. Andrew Clement b, Haytham Kubba b,*aUniversity of Glasgow, United KingdombDepartment of Otolaryngology – Head and Neck Surgery, Royal Hospital for Sick Children, Glasgow G3 8SJ, Scotland, United Kingdom

A R T I C L E I N F O

Article history:Received 17 February 2014Received in revised form 21 May 2014Accepted 25 May 2014Available online 19 June 2014

Keywords:Cornelia de LangeSupraglottoplastyAirwayOtolaryngology

A B S T R A C T

Aim: Children with Cornelia de Lange syndrome frequently present to otolaryngology services withhearing problems. Airway problems have not previously been reported. We wish to describe ourexperience of the overall management in a series of children with Cornelia de Lange syndrome.Methods: Retrospective case note review of children diagnosed with Cornelia de Lange syndromepresenting to our department between 2005 and 2014.Results: Six patients were seen. Airway problems consisted of laryngeal overspill with severegastroesophageal dysmotility and reflux despite structurally normal airway (1 case), laryngomalaciarequiring supraglottoplasty (2 cases), reflux laryngitis with secondary laryngomalacia and coincidentaltracheal diverticulum (1 case) choanal atresia requiring stents (1 case) and obstructive sleep apnoea (1case). Supraglottoplasty produced a dramatic improvement in feeding and breathing in both childrenwho underwent the procedure. Two children had palatal anomalies and one underwent cochlearimplantation for a profound sensorineural hearing loss.Conclusion: Children with Cornelia de Lange syndrome have multifaceted ENT problems. Airwaypathology has not previously been described in Cornelia de Lange syndrome but has been common in ourexperience. We wish to highlight that laryngomalacia in Cornelia de Lange syndrome responds well tosupraglottoplasty.

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Introduction

Cornelia de Lange syndrome, also known as Brachmann-deLange syndrome, is a rare autosomal dominant developmentaldisorder featuring multiple congenital abnormalities, small statureand mental retardation. It has a reported incidence of 1/10,000births [1]. The exact incidence may however be higher as a muchmilder phenotype is now being increasingly recognised [2].

Initially the diagnosis of Cornelia de Lange syndrome is madeclinically, with confirmation on genetic testing. The genes NIPBL(50–60% of cases) [3–5], SMC1A and SMC3 (5% of cases) [6] have allbeen found to cause Cornelia de Lange syndrome.

The main clinical features of Cornelia de Lange syndromepresent in the gastrointestinal, cardiovascular, neurological,musculoskeletal and craniofacial systems, and vary from mild tosevere. Gastrointestinal symptoms including feeding difficultiesand gastro-oesophageal reflux disease are common, with associ-ated Barrett's oesophagus being found in 10% of patients with this

* Corresponding author. Tel.: +44 141 2010297; fax: +44 141 2010865.E-mail address: hkubba@nhs.net (H. Kubba).

http://dx.doi.org/10.1016/j.ijporl.2014.05.0320165-5876/ã 2014 Elsevier Ireland Ltd. All rights reserved.

syndrome [7]. Congenital cardiac septal defects are also commonlyreported as are absent forearms and digits [8].

The craniofacial appearance of these children is most charac-teristic with features including microbrachycephaly, synophrys[10], long and thick eyelashes, low set ears, a small upturned nose,a high arched palate with cleft palate in 30% [9], small widely-spaced teeth, a short neck and micrognathia [8]. Hearingdifficulties are also reported in the majority of cases as there areusually middle ear effusions and stenosis of the external auditorycanals [11].

Children with Cornelia de Lange syndrome frequently presentto ENT services with hearing problems as described above. Airwayproblems in Cornelia de Lange syndrome have not previously beenreported, however difficulty on intubating these children has beennoted [14–16]. The aim of this study is to describe, review andreport on our experience of the airway management of thesechildren.

Methods

A retrospective case note review of all children diagnosed withCornelia de Lange syndrome presenting to the Royal Hospital for

J. Hamilton et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 1548–1550 1549

Sick Children, Glasgow between 2005 and 2014 was undertaken.All otolaryngological symptoms, signs, investigations and treat-ments were identified.

Cases

Case 1A twenty-two year old male, with known Cornelia de Lange

syndrome, presented with a long-standing problem of oesophagealdysmotility with gastro-oesophageal reflux disease giving rise tooverspill into the larynx with choking attacks, despite fundopli-cation, gastrostomy and anti-reflux medication. Microlaryngo-bronchoscopy showed pachydermia of the posterior larynx,cobblestoning of the mucosa and blunting of the carina,demonstrated an airway with signs consistent with gastro-oesophageal reflux disease and overspill. There was no evidenceor history of any hearing problems.

Case 2A twenty-month old female, with known Cornelia de Lange

syndrome, was referred for investigation with a view to cochlearimplantation. She was known to have a bilateral profoundsensorineural hearing impairment and also had breathingdifficulties. She underwent airway examination at the time of ageneral anaesthetic for MRI and CT scans, to exclude any significantairway pathology. Findings at surgery included a submucosal cleftpalate, bifid uvula, notched hard palate, prominent lingual tonsilsand large palatine tonsils. Microlaryngobronchoscopy demon-strated findings consistent with laryngomalacia and a right-sidedblind ending tracheal pouch just above the carina. Clinically herstridor was intermittent and positional but not causing her anydistress therefore no treatment was undertaken. She thensuccessfully underwent a bilateral cochlear implantation. Shehas subsequently developed clinical features of obstructive sleepapnoea and is currently undergoing investigation with a view toadenotonsillectomy and lingual tonsil ablation.

Case 3A four year old male, with known Cornelia de Lange syndrome,

presented with nasal obstruction and heavy snoring. Flexibleendoscopy demonstrated occlusive adenoids and laryngomalacia.He had a very short soft palate with bifid uvula and poor palatalelevation and symptoms of nasal regurgitation. He was also knownto have severe reflux with associated Barrett's oesophagus.Following discussion with his parents regarding the potential riskof worsening his velopharyngeal incompetence with adenoidec-tomy they elected for ongoing conservative management. His nasalobstruction became less over a follow up period of seven years, ashis adenoids gradually atrophied, but unfortunately during this

Table 1Cornelia de Lange Syndrome cases.

Case Age atpresentation

Main PC Hearing

1 22 years GORD and laryngeal overspill N/A

2 20 months Cochlear implantation, noisybreathing

Bilateral sensorineuralimpairment

3 4 years Nasal obstruction, snoring, VPI N/A

4 12 weeks Stridor, breathing difficulties Mild/moderate hearing

5 8 weeks Stridor, noisy breathing Moderate/severe hearing

6 4 weeks Cyanosis and respiratory distress N/A

time his velopharyngeal incompetence worsened. He has ongoingreview with the Cleft Palate Service but no surgery is planned atpresent.

Case 4A twelve-week old male was referred with inspiratory stridor,

feeding difficulties and failure to thrive. He had dysmorphicfeatures typical of Cornelia de Lange syndrome including hyper-telorism, Pierre Robin sequence, single palmar crease, shalloworbits, thin lips and micrognathia. This lead to a clinical diagnosisof Cornelia de Lange syndrome. His palate was intact. He was alsodiagnosed with mild/moderate hearing loss and had narrow earcanals during this admission. He underwent microlaryngobron-choscopy which confirmed laryngomalacia and gastro-oesopha-geal reflux disease and underwent supraglottoplasty under thesame anaesthetic: incision of both aryepiglottic folds with a laserepiglottopexy [17]. Post-operatively he struggled following extu-bation and required a short period of support with a nasopharyn-geal airway. He recovered well only having intermittent stridor onfeeding. Although his stridor remained at six months he wasgrowing appropriately for a child with Cornelia de Langesyndrome. He was discharged to local Paediatric Services at thistime Table 1.

Case 5An eight-week old female presented with stridor, significantly

increased work of breathing, feeding difficulties and failure tothrive. There were concerns regarding her hearing as she had failedtwo hearing screening tests. A diagnosis of Cornelia de Langesyndrome was suspected on clinical grounds due to dysmorphicfeatures. Microlaryngobronchoscopy was consistent with laryng-omalacia and supraglottoplasty in the form of a simple aryepiglot-tic fold incision was therefore undertaken. Clinically following this,almost complete resolution of the stridor occurred. This wassupported by an obvious improvement in her overnight pulse-oximetry sleep study: 137–27 desaturations per hour, as demon-strated in Fig. 1.

Case 6A four-week old male presented to our department with

cyanosis and respiratory distress, previous hypoxic ischaemicencephalopathy, dysmorphic features and a clinical diagnosis ofCornelia de Lange syndrome. Upon microlaryngobronchoscopy hewas found to have very mild tracheomalacia and bilateral choanalatresia. He underwent surgery for the choanal atresia, whichinvolved perforating, drilling and placing bilateral stents. Theseremained in for six weeks. Upon removal however, the patientbegan to struggle with almost complete choanal occlusion and scartissue formation. Nasal stents were placed again and will remain in

Airway Cleft palate Airway surgery

Findings consistent with GORD andoverspill

No N

Laryngomalacia Yes N

Laryngomalacia Submucousalcleft

N

loss Laryngomalacia No YSupraglottoplasty

loss Laryngomalacia No YSupraglottoplasty

Laryngomalacia No YChoanal stenting

Fig. 1. Before and after results of sleep study.

1550 J. Hamilton et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 1548–1550

for another six-week period. On each occasion 5 mm airwayballoons were used and a 3.5 mm endotracheal tube was fashionedto form the nasal stents. The repeat microlaryngobronchoscopyshowed no further tracheomalacia.

Discussion

Children with Cornelia de Lange syndrome present to PaediatricOtolaryngologists with multi-faceted problems, most commonlyrelating to hearing. Airway pathology has not previously beendescribed in these children but is common in our experience. AMedline search was unable to identify any other papers thatidentified this presumed association although intubation difficul-ties have been reported in these children [12]. Poorer outcomes arefrequently reported in the management of laryngomalacia forsyndromal children with associated co-morbidities [13]. We wishto highlight that airway pathology was common in our small seriesof children with Cornelia de Lange syndrome and that laryngo-malacia responded well to surgical interventions.

Ethical approval

Registered with Clinical Governance Committee.

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