International Journal of Pediatric Otorhinolaryngology 78 (2014) 1548–1550
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case report
Otolaryngological presentations of Cornelia de Lange syndrome Jane Hamilton a , W. Andrew Clement b , Haytham Kubba b, * a b
University of Glasgow, United Kingdom Department 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
A B S T R A C T
Article history: Received 17 February 2014 Received in revised form 21 May 2014 Accepted 25 May 2014 Available online 19 June 2014
Aim: Children with Cornelia de Lange syndrome frequently present to otolaryngology services with hearing problems. Airway problems have not previously been reported. We wish to describe our experience 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 syndrome presenting to our department between 2005 and 2014. Results: Six patients were seen. Airway problems consisted of laryngeal overspill with severe gastroesophageal dysmotility and reflux despite structurally normal airway (1 case), laryngomalacia requiring supraglottoplasty (2 cases), reflux laryngitis with secondary laryngomalacia and coincidental tracheal diverticulum (1 case) choanal atresia requiring stents (1 case) and obstructive sleep apnoea (1 case). Supraglottoplasty produced a dramatic improvement in feeding and breathing in both children who underwent the procedure. Two children had palatal anomalies and one underwent cochlear implantation for a profound sensorineural hearing loss. Conclusion: Children with Cornelia de Lange syndrome have multifaceted ENT problems. Airway pathology has not previously been described in Cornelia de Lange syndrome but has been common in our experience. We wish to highlight that laryngomalacia in Cornelia de Lange syndrome responds well to supraglottoplasty. ã 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cornelia de Lange Supraglottoplasty Airway Otolaryngology
Introduction Cornelia de Lange syndrome, also known as Brachmann-de Lange syndrome, is a rare autosomal dominant developmental disorder featuring multiple congenital abnormalities, small stature and mental retardation. It has a reported incidence of 1/10,000 births [1]. The exact incidence may however be higher as a much milder phenotype is now being increasingly recognised [2]. Initially the diagnosis of Cornelia de Lange syndrome is made clinically, with confirmation on genetic testing. The genes NIPBL (50–60% of cases) [3–5], SMC1A and SMC3 (5% of cases) [6] have all been found to cause Cornelia de Lange syndrome. The main clinical features of Cornelia de Lange syndrome present in the gastrointestinal, cardiovascular, neurological, musculoskeletal and craniofacial systems, and vary from mild to severe. Gastrointestinal symptoms including feeding difficulties and gastro-oesophageal reflux disease are common, with associated Barrett's oesophagus being found in 10% of patients with this
syndrome [7]. Congenital cardiac septal defects are also commonly reported as are absent forearms and digits [8]. The craniofacial appearance of these children is most characteristic 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 widelyspaced teeth, a short neck and micrognathia [8]. Hearing difficulties are also reported in the majority of cases as there are usually middle ear effusions and stenosis of the external auditory canals [11]. Children with Cornelia de Lange syndrome frequently present to ENT services with hearing problems as described above. Airway problems in Cornelia de Lange syndrome have not previously been reported, however difficulty on intubating these children has been noted [14–16]. The aim of this study is to describe, review and report on our experience of the airway management of these children. Methods
* Corresponding author. Tel.: +44 141 2010297; fax: +44 141 2010865. E-mail address: [email protected] (H. Kubba). http://dx.doi.org/10.1016/j.ijporl.2014.05.032 0165-5876/ ã 2014 Elsevier Ireland Ltd. All rights reserved.
A retrospective case note review of all children diagnosed with Cornelia 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 treatments were identified.
time his velopharyngeal incompetence worsened. He has ongoing review with the Cleft Palate Service but no surgery is planned at present.
Cases
Case 4 A twelve-week old male was referred with inspiratory stridor, feeding difficulties and failure to thrive. He had dysmorphic features typical of Cornelia de Lange syndrome including hypertelorism, Pierre Robin sequence, single palmar crease, shallow orbits, thin lips and micrognathia. This lead to a clinical diagnosis of Cornelia de Lange syndrome. His palate was intact. He was also diagnosed with mild/moderate hearing loss and had narrow ear canals during this admission. He underwent microlaryngobronchoscopy which confirmed laryngomalacia and gastro-oesophageal reflux disease and underwent supraglottoplasty under the same anaesthetic: incision of both aryepiglottic folds with a laser epiglottopexy [17]. Post-operatively he struggled following extubation and required a short period of support with a nasopharyngeal airway. He recovered well only having intermittent stridor on feeding. Although his stridor remained at six months he was growing appropriately for a child with Cornelia de Lange syndrome. He was discharged to local Paediatric Services at this time Table 1.
Case 1 A twenty-two year old male, with known Cornelia de Lange syndrome, presented with a long-standing problem of oesophageal dysmotility with gastro-oesophageal reflux disease giving rise to overspill into the larynx with choking attacks, despite fundoplication, gastrostomy and anti-reflux medication. Microlaryngobronchoscopy showed pachydermia of the posterior larynx, cobblestoning of the mucosa and blunting of the carina, demonstrated an airway with signs consistent with gastrooesophageal reflux disease and overspill. There was no evidence or history of any hearing problems. Case 2 A twenty-month old female, with known Cornelia de Lange syndrome, was referred for investigation with a view to cochlear implantation. She was known to have a bilateral profound sensorineural hearing impairment and also had breathing difficulties. She underwent airway examination at the time of a general anaesthetic for MRI and CT scans, to exclude any significant airway pathology. Findings at surgery included a submucosal cleft palate, bifid uvula, notched hard palate, prominent lingual tonsils and large palatine tonsils. Microlaryngobronchoscopy demonstrated findings consistent with laryngomalacia and a right-sided blind ending tracheal pouch just above the carina. Clinically her stridor was intermittent and positional but not causing her any distress therefore no treatment was undertaken. She then successfully underwent a bilateral cochlear implantation. She has subsequently developed clinical features of obstructive sleep apnoea and is currently undergoing investigation with a view to adenotonsillectomy and lingual tonsil ablation. Case 3 A four year old male, with known Cornelia de Lange syndrome, presented with nasal obstruction and heavy snoring. Flexible endoscopy demonstrated occlusive adenoids and laryngomalacia. He had a very short soft palate with bifid uvula and poor palatal elevation and symptoms of nasal regurgitation. He was also known to have severe reflux with associated Barrett's oesophagus. Following discussion with his parents regarding the potential risk of worsening his velopharyngeal incompetence with adenoidectomy they elected for ongoing conservative management. His nasal obstruction became less over a follow up period of seven years, as his adenoids gradually atrophied, but unfortunately during this
Case 5 An eight-week old female presented with stridor, significantly increased work of breathing, feeding difficulties and failure to thrive. There were concerns regarding her hearing as she had failed two hearing screening tests. A diagnosis of Cornelia de Lange syndrome was suspected on clinical grounds due to dysmorphic features. Microlaryngobronchoscopy was consistent with laryngomalacia and supraglottoplasty in the form of a simple aryepiglottic fold incision was therefore undertaken. Clinically following this, almost complete resolution of the stridor occurred. This was supported by an obvious improvement in her overnight pulseoximetry sleep study: 137–27 desaturations per hour, as demonstrated in Fig. 1. Case 6 A four-week old male presented to our department with cyanosis and respiratory distress, previous hypoxic ischaemic encephalopathy, dysmorphic features and a clinical diagnosis of Cornelia de Lange syndrome. Upon microlaryngobronchoscopy he was found to have very mild tracheomalacia and bilateral choanal atresia. He underwent surgery for the choanal atresia, which involved perforating, drilling and placing bilateral stents. These remained in for six weeks. Upon removal however, the patient began to struggle with almost complete choanal occlusion and scar tissue formation. Nasal stents were placed again and will remain in
Table 1 Cornelia de Lange Syndrome cases. Case
Age at presentation
Main PC
Hearing
Airway
Cleft palate
Airway surgery
1
22 years
GORD and laryngeal overspill
N/A
No
N
2
20 months
N
4 years
Bilateral sensorineural impairment N/A
Yes
3
Cochlear implantation, noisy breathing Nasal obstruction, snoring, VPI
Findings consistent with GORD and overspill Laryngomalacia Laryngomalacia
N
4
12 weeks
Stridor, breathing difficulties
Mild/moderate hearing loss
Submucousal cleft No
5
8 weeks
Stridor, noisy breathing
Moderate/severe hearing loss Laryngomalacia
6
4 weeks
Cyanosis and respiratory distress N/A
Laryngomalacia
Laryngomalacia
No No
Y Supraglottoplasty Y Supraglottoplasty Y Choanal stenting
1550
J. Hamilton et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 1548–1550
References
Fig. 1. Before and after results of sleep study.
for another six-week period. On each occasion 5 mm airway balloons were used and a 3.5 mm endotracheal tube was fashioned to form the nasal stents. The repeat microlaryngobronchoscopy showed no further tracheomalacia. Discussion Children with Cornelia de Lange syndrome present to Paediatric Otolaryngologists with multi-faceted problems, most commonly relating to hearing. Airway pathology has not previously been described in these children but is common in our experience. A Medline search was unable to identify any other papers that identified this presumed association although intubation difficulties have been reported in these children [12]. Poorer outcomes are frequently reported in the management of laryngomalacia for syndromal children with associated co-morbidities [13]. We wish to highlight that airway pathology was common in our small series of children with Cornelia de Lange syndrome and that laryngomalacia responded well to surgical interventions. Ethical approval Registered with Clinical Governance Committee.
[1] J.M. Opitz, The Brachmann-de Lange syndrome, Am. J. Med. Genet. 22 (1985) 89–102. [2] A.D. Kline, I.D. Krantz, A. Sommer, M. Kliewer, L.G. Jackson, D.R. FitzPatrick, A.V. Levin, A. Selicorni, Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance, Am. J. Med. Genet. Part A 14 (2007) 1287–1296. [3] L.A. Gillis, J. McCallum, M. Kaur, C. DeScipio, D. Yaeger, A. Mariani, A.D. Kline, H. H. Li, M. Devoto, L.G. Jackson, I.D. Krantz, NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotypephenotype correlations, Am. J. Hum. Genet. 75 (2004) 610–623. [4] Z.A. Bhuiyan, M. Klein, P. Hammond, A. van Haeringen, M.M. Mannens, I. Van Berckelaer-Onnes, R.C. Hennekam, Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience, J. Med. Genet. 43 (2006) 568–575. [5] G. Borck, R. Redon, D. Sanlaville, M. Rio, M. Prieur, S. Lyonnet, M. Vekemans, N. P. Carter, A. Munnich, L. Colleaux, V. Cormier-Daire, NIPBL mutations and genetic heterogeneity in Cornelia de Lange syndrome, J. Med. Genet. 41 (2004) e128. [6] M.A. Deardorff, M. Kaur, D. Yaeger, A. Rampuria, S. Korolev, J. Pie, C. GilRodríguez, M. Arnedo, B. Loeys, A.D. Kline, M. Wilson, K. Lillquist, V. Siu, F.J. Ramos, A. Musio, L.S. Jackson, D. Dorsett, I.D. Krantz, Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation, Am. J. Hum. Genet. 80 (2007) 485–494. [7] A.D. Kline, M. Grados, P. Sponseller, H.P. Levy, N. Blagowidow, C. Schoedel, J. Rampolla, D.K. Clemens, I. Krantz, A. Kimball, C. Pichard, D. Tuchman, Natural history of aging in Cornelia de Lange syndrome, Am. J. Med. Genet. C Semin. Med. Genet. 14 (2007) 248–260. [8] V. Washington, A.D. Kaye, Anesthetic management in a patient with Cornelia de Lange syndrome, Middle East J. Anesthesiol. 20 (6) (2010) 773–778. [9] R.T. Sataloff, J.R. Spiegel, M. Hawkshaw, J.M. Epstein, L. Jackson, Cornelia de Lange syndrome. Otolaryngologic manifestations, Arch. Otolaryngol. Head Neck Surg. 116 (1990) 1044–1046. [10] L. Jackson, A.D. Kline, M.A. Barr, S. Koch, de Lange syndrome: a clinical review of 310 individuals, Am. J. Med. Genet. 47 (1993) 940–946. [11] P. Marchisio, A. Selicorni, L. Pignataro, D. Milani, E. Baggi, L. Lambertini, E. Dusi, L. Villa, P. Capaccio, M. Cerutti, S. Esposito, N. Principi, Otitis media with effusion and hearing loss in children with Cornelia de Lange syndrome, Am. J. Med. Genet. 146A (2008) 426–432. [12] D.A. August, S. Sorhabi, Is a difficult airway predictable in Cornelia de Lange syndrome? Paediatr. Anaesth. 19 (July (7)) (2009) 707–709. [13] S.R. Hoff, J.W. Schroeder Jr, J.C. Rastatter, L.D. Holinger, Supraglottoplasty outcomes in relation to age and comorbid conditions, Int. J. Pediatr. Otorhinolaryngol. 74 (3) (2010) 245–249. [14] T. Sugiyama, R. Okutani, Difficult tracheal intubation in a child with Cornelia de Lange syndrome using a paediatric Intlock installed in a Pentax Airway Scope, Anaesthesia 67 (December (12)) (2012) 1411–1412. [15] Y. Tsukazaki, C. Tachibana, K. Satoh, T. Fukada, Y. Ohe, A patient with Cornelia de Lange syndrome with difficulty in orotracheal intubation, Masui 45 (August (8)) (1996) 991–993. [16] M.F. Struck, J. Seifert, A. Rümmler, A. Nowak, To intubate or not to intubate: Cornelia de Lange syndrome, ileus and helicopter transport, Eur. J. Emerg. Med. 19 (April (2)) (2012) 126–127. [17] A.D. Whymark, W.A. Clement, H. Kubba, N.K. Geddes, Laser epiglottopexy for laryngomalacia: 10 years' experience in the west of Scotland, Arch. Otolaryngol. Head Neck Surg. 132 (September (9)) (2006) 978–982.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case report
Otolaryngological presentations of Cornelia de Lange syndrome Jane Hamilton a , W. Andrew Clement b , Haytham Kubba b, * a b
University of Glasgow, United Kingdom Department 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
A B S T R A C T
Article history: Received 17 February 2014 Received in revised form 21 May 2014 Accepted 25 May 2014 Available online 19 June 2014
Aim: Children with Cornelia de Lange syndrome frequently present to otolaryngology services with hearing problems. Airway problems have not previously been reported. We wish to describe our experience 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 syndrome presenting to our department between 2005 and 2014. Results: Six patients were seen. Airway problems consisted of laryngeal overspill with severe gastroesophageal dysmotility and reflux despite structurally normal airway (1 case), laryngomalacia requiring supraglottoplasty (2 cases), reflux laryngitis with secondary laryngomalacia and coincidental tracheal diverticulum (1 case) choanal atresia requiring stents (1 case) and obstructive sleep apnoea (1 case). Supraglottoplasty produced a dramatic improvement in feeding and breathing in both children who underwent the procedure. Two children had palatal anomalies and one underwent cochlear implantation for a profound sensorineural hearing loss. Conclusion: Children with Cornelia de Lange syndrome have multifaceted ENT problems. Airway pathology has not previously been described in Cornelia de Lange syndrome but has been common in our experience. We wish to highlight that laryngomalacia in Cornelia de Lange syndrome responds well to supraglottoplasty. ã 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Cornelia de Lange Supraglottoplasty Airway Otolaryngology
Introduction Cornelia de Lange syndrome, also known as Brachmann-de Lange syndrome, is a rare autosomal dominant developmental disorder featuring multiple congenital abnormalities, small stature and mental retardation. It has a reported incidence of 1/10,000 births [1]. The exact incidence may however be higher as a much milder phenotype is now being increasingly recognised [2]. Initially the diagnosis of Cornelia de Lange syndrome is made clinically, with confirmation on genetic testing. The genes NIPBL (50–60% of cases) [3–5], SMC1A and SMC3 (5% of cases) [6] have all been found to cause Cornelia de Lange syndrome. The main clinical features of Cornelia de Lange syndrome present in the gastrointestinal, cardiovascular, neurological, musculoskeletal and craniofacial systems, and vary from mild to severe. Gastrointestinal symptoms including feeding difficulties and gastro-oesophageal reflux disease are common, with associated Barrett's oesophagus being found in 10% of patients with this
syndrome [7]. Congenital cardiac septal defects are also commonly reported as are absent forearms and digits [8]. The craniofacial appearance of these children is most characteristic 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 widelyspaced teeth, a short neck and micrognathia [8]. Hearing difficulties are also reported in the majority of cases as there are usually middle ear effusions and stenosis of the external auditory canals [11]. Children with Cornelia de Lange syndrome frequently present to ENT services with hearing problems as described above. Airway problems in Cornelia de Lange syndrome have not previously been reported, however difficulty on intubating these children has been noted [14–16]. The aim of this study is to describe, review and report on our experience of the airway management of these children. Methods
* Corresponding author. Tel.: +44 141 2010297; fax: +44 141 2010865. E-mail address: [email protected] (H. Kubba). http://dx.doi.org/10.1016/j.ijporl.2014.05.032 0165-5876/ ã 2014 Elsevier Ireland Ltd. All rights reserved.
A retrospective case note review of all children diagnosed with Cornelia 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 treatments were identified.
time his velopharyngeal incompetence worsened. He has ongoing review with the Cleft Palate Service but no surgery is planned at present.
Cases
Case 4 A twelve-week old male was referred with inspiratory stridor, feeding difficulties and failure to thrive. He had dysmorphic features typical of Cornelia de Lange syndrome including hypertelorism, Pierre Robin sequence, single palmar crease, shallow orbits, thin lips and micrognathia. This lead to a clinical diagnosis of Cornelia de Lange syndrome. His palate was intact. He was also diagnosed with mild/moderate hearing loss and had narrow ear canals during this admission. He underwent microlaryngobronchoscopy which confirmed laryngomalacia and gastro-oesophageal reflux disease and underwent supraglottoplasty under the same anaesthetic: incision of both aryepiglottic folds with a laser epiglottopexy [17]. Post-operatively he struggled following extubation and required a short period of support with a nasopharyngeal airway. He recovered well only having intermittent stridor on feeding. Although his stridor remained at six months he was growing appropriately for a child with Cornelia de Lange syndrome. He was discharged to local Paediatric Services at this time Table 1.
Case 1 A twenty-two year old male, with known Cornelia de Lange syndrome, presented with a long-standing problem of oesophageal dysmotility with gastro-oesophageal reflux disease giving rise to overspill into the larynx with choking attacks, despite fundoplication, gastrostomy and anti-reflux medication. Microlaryngobronchoscopy showed pachydermia of the posterior larynx, cobblestoning of the mucosa and blunting of the carina, demonstrated an airway with signs consistent with gastrooesophageal reflux disease and overspill. There was no evidence or history of any hearing problems. Case 2 A twenty-month old female, with known Cornelia de Lange syndrome, was referred for investigation with a view to cochlear implantation. She was known to have a bilateral profound sensorineural hearing impairment and also had breathing difficulties. She underwent airway examination at the time of a general anaesthetic for MRI and CT scans, to exclude any significant airway pathology. Findings at surgery included a submucosal cleft palate, bifid uvula, notched hard palate, prominent lingual tonsils and large palatine tonsils. Microlaryngobronchoscopy demonstrated findings consistent with laryngomalacia and a right-sided blind ending tracheal pouch just above the carina. Clinically her stridor was intermittent and positional but not causing her any distress therefore no treatment was undertaken. She then successfully underwent a bilateral cochlear implantation. She has subsequently developed clinical features of obstructive sleep apnoea and is currently undergoing investigation with a view to adenotonsillectomy and lingual tonsil ablation. Case 3 A four year old male, with known Cornelia de Lange syndrome, presented with nasal obstruction and heavy snoring. Flexible endoscopy demonstrated occlusive adenoids and laryngomalacia. He had a very short soft palate with bifid uvula and poor palatal elevation and symptoms of nasal regurgitation. He was also known to have severe reflux with associated Barrett's oesophagus. Following discussion with his parents regarding the potential risk of worsening his velopharyngeal incompetence with adenoidectomy they elected for ongoing conservative management. His nasal obstruction became less over a follow up period of seven years, as his adenoids gradually atrophied, but unfortunately during this
Case 5 An eight-week old female presented with stridor, significantly increased work of breathing, feeding difficulties and failure to thrive. There were concerns regarding her hearing as she had failed two hearing screening tests. A diagnosis of Cornelia de Lange syndrome was suspected on clinical grounds due to dysmorphic features. Microlaryngobronchoscopy was consistent with laryngomalacia and supraglottoplasty in the form of a simple aryepiglottic fold incision was therefore undertaken. Clinically following this, almost complete resolution of the stridor occurred. This was supported by an obvious improvement in her overnight pulseoximetry sleep study: 137–27 desaturations per hour, as demonstrated in Fig. 1. Case 6 A four-week old male presented to our department with cyanosis and respiratory distress, previous hypoxic ischaemic encephalopathy, dysmorphic features and a clinical diagnosis of Cornelia de Lange syndrome. Upon microlaryngobronchoscopy he was found to have very mild tracheomalacia and bilateral choanal atresia. He underwent surgery for the choanal atresia, which involved perforating, drilling and placing bilateral stents. These remained in for six weeks. Upon removal however, the patient began to struggle with almost complete choanal occlusion and scar tissue formation. Nasal stents were placed again and will remain in
Table 1 Cornelia de Lange Syndrome cases. Case
Age at presentation
Main PC
Hearing
Airway
Cleft palate
Airway surgery
1
22 years
GORD and laryngeal overspill
N/A
No
N
2
20 months
N
4 years
Bilateral sensorineural impairment N/A
Yes
3
Cochlear implantation, noisy breathing Nasal obstruction, snoring, VPI
Findings consistent with GORD and overspill Laryngomalacia Laryngomalacia
N
4
12 weeks
Stridor, breathing difficulties
Mild/moderate hearing loss
Submucousal cleft No
5
8 weeks
Stridor, noisy breathing
Moderate/severe hearing loss Laryngomalacia
6
4 weeks
Cyanosis and respiratory distress N/A
Laryngomalacia
Laryngomalacia
No No
Y Supraglottoplasty Y Supraglottoplasty Y Choanal stenting
1550
J. Hamilton et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 1548–1550
References
Fig. 1. Before and after results of sleep study.
for another six-week period. On each occasion 5 mm airway balloons were used and a 3.5 mm endotracheal tube was fashioned to form the nasal stents. The repeat microlaryngobronchoscopy showed no further tracheomalacia. Discussion Children with Cornelia de Lange syndrome present to Paediatric Otolaryngologists with multi-faceted problems, most commonly relating to hearing. Airway pathology has not previously been described in these children but is common in our experience. A Medline search was unable to identify any other papers that identified this presumed association although intubation difficulties have been reported in these children [12]. Poorer outcomes are frequently reported in the management of laryngomalacia for syndromal children with associated co-morbidities [13]. We wish to highlight that airway pathology was common in our small series of children with Cornelia de Lange syndrome and that laryngomalacia responded well to surgical interventions. Ethical approval Registered with Clinical Governance Committee.
[1] J.M. Opitz, The Brachmann-de Lange syndrome, Am. J. Med. Genet. 22 (1985) 89–102. [2] A.D. Kline, I.D. Krantz, A. Sommer, M. Kliewer, L.G. Jackson, D.R. FitzPatrick, A.V. Levin, A. Selicorni, Cornelia de Lange syndrome: clinical review, diagnostic and scoring systems, and anticipatory guidance, Am. J. Med. Genet. Part A 14 (2007) 1287–1296. [3] L.A. Gillis, J. McCallum, M. Kaur, C. DeScipio, D. Yaeger, A. Mariani, A.D. Kline, H. H. Li, M. Devoto, L.G. Jackson, I.D. Krantz, NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotypephenotype correlations, Am. J. Hum. Genet. 75 (2004) 610–623. [4] Z.A. Bhuiyan, M. Klein, P. Hammond, A. van Haeringen, M.M. Mannens, I. Van Berckelaer-Onnes, R.C. Hennekam, Genotype-phenotype correlations of 39 patients with Cornelia De Lange syndrome: the Dutch experience, J. Med. Genet. 43 (2006) 568–575. [5] G. Borck, R. Redon, D. Sanlaville, M. Rio, M. Prieur, S. Lyonnet, M. Vekemans, N. P. Carter, A. Munnich, L. Colleaux, V. Cormier-Daire, NIPBL mutations and genetic heterogeneity in Cornelia de Lange syndrome, J. Med. Genet. 41 (2004) e128. [6] M.A. Deardorff, M. Kaur, D. Yaeger, A. Rampuria, S. Korolev, J. Pie, C. GilRodríguez, M. Arnedo, B. Loeys, A.D. Kline, M. Wilson, K. Lillquist, V. Siu, F.J. Ramos, A. Musio, L.S. Jackson, D. Dorsett, I.D. Krantz, Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation, Am. J. Hum. Genet. 80 (2007) 485–494. [7] A.D. Kline, M. Grados, P. Sponseller, H.P. Levy, N. Blagowidow, C. Schoedel, J. Rampolla, D.K. Clemens, I. Krantz, A. Kimball, C. Pichard, D. Tuchman, Natural history of aging in Cornelia de Lange syndrome, Am. J. Med. Genet. C Semin. Med. Genet. 14 (2007) 248–260. [8] V. Washington, A.D. Kaye, Anesthetic management in a patient with Cornelia de Lange syndrome, Middle East J. Anesthesiol. 20 (6) (2010) 773–778. [9] R.T. Sataloff, J.R. Spiegel, M. Hawkshaw, J.M. Epstein, L. Jackson, Cornelia de Lange syndrome. Otolaryngologic manifestations, Arch. Otolaryngol. Head Neck Surg. 116 (1990) 1044–1046. [10] L. Jackson, A.D. Kline, M.A. Barr, S. Koch, de Lange syndrome: a clinical review of 310 individuals, Am. J. Med. Genet. 47 (1993) 940–946. [11] P. Marchisio, A. Selicorni, L. Pignataro, D. Milani, E. Baggi, L. Lambertini, E. Dusi, L. Villa, P. Capaccio, M. Cerutti, S. Esposito, N. Principi, Otitis media with effusion and hearing loss in children with Cornelia de Lange syndrome, Am. J. Med. Genet. 146A (2008) 426–432. [12] D.A. August, S. Sorhabi, Is a difficult airway predictable in Cornelia de Lange syndrome? Paediatr. Anaesth. 19 (July (7)) (2009) 707–709. [13] S.R. Hoff, J.W. Schroeder Jr, J.C. Rastatter, L.D. Holinger, Supraglottoplasty outcomes in relation to age and comorbid conditions, Int. J. Pediatr. Otorhinolaryngol. 74 (3) (2010) 245–249. [14] T. Sugiyama, R. Okutani, Difficult tracheal intubation in a child with Cornelia de Lange syndrome using a paediatric Intlock installed in a Pentax Airway Scope, Anaesthesia 67 (December (12)) (2012) 1411–1412. [15] Y. Tsukazaki, C. Tachibana, K. Satoh, T. Fukada, Y. Ohe, A patient with Cornelia de Lange syndrome with difficulty in orotracheal intubation, Masui 45 (August (8)) (1996) 991–993. [16] M.F. Struck, J. Seifert, A. Rümmler, A. Nowak, To intubate or not to intubate: Cornelia de Lange syndrome, ileus and helicopter transport, Eur. J. Emerg. Med. 19 (April (2)) (2012) 126–127. [17] A.D. Whymark, W.A. Clement, H. Kubba, N.K. Geddes, Laser epiglottopexy for laryngomalacia: 10 years' experience in the west of Scotland, Arch. Otolaryngol. Head Neck Surg. 132 (September (9)) (2006) 978–982.
