Syndromic choanal atresia: The example of CHARGE Syndrome

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1 CASE REPORT Syndromic choanal atresia: The example of CHARGE Syndrome R. Bechraoui, S. Jbali, M. Tebini, M. Dhaha, H. Chahed, A. Mediouni, M. Ben Amor, N. Beltaief, R. Zainine, G. Besbes. Ear, nose and throat and CMF department of La Rabta hospital, Tunis, Tunisia. Tunis Medicine Faculty, Tunis, Tunisia. SUMMARY Introduction: Uni or bilateral congenital narrowing of the choanae is an uncommon condition in pediatric patients. The surgical management in cases of choanal atresia varies widely in different centers. This management is certainly urgent in cases of bilateral choanal atresia. Otherwise, it is part of a global management in case of syndromic choanal atresia. In this article, we deal with the example of CHARGE syndrome. Observations: We report 3 cases of CHARGE syndrome treated in our department. Choanal atresia was bilateral in 2 cases.the management of the choanal atresia, however, was delayed in one case where it was unilateral.coloboma was diagnosed in one case, Heart defect in one case, Atresia, Growth retardation in one case, Genital hypoplasia in 3 cases and Ear anomalies in 2 cases. Conclusion: CHARGE syndrom is a serious disease and the overall outcome and survival may be improved only if there is good collaboration between specialists of different fields. Key words: Choanal atresia, CHARGE syndrome, Newborn, Endoscopic approach, Trans-palatal approach, Stenting. INTRODUCTION First described in 1979 by Hall and Hittner et al, CHARGE syndrome was initially defined as a non-random association of anomalies. The acronym CHARGE stands for the major features of this syndrome: Coloboma, Heart defects, Choanal Atresia., growth retardation, Genital hypoplasia and Ear anomalies and/or deafness [1]. The CHARGE syndrome is considered to be a recognizable syndrome with genetic basis. Its phenotype may be related to CHD7 gene mutations [2]. Choanal atresia is one of the four major diagnostic criteria of this syndrome. Main differential diagnoses are the VACTERL association, DiGeorge sequence, 22q11 micro deletion, PAX2 abnormalities and retinoic acid embryopathy. This syndrome has a poor prognosis which depends mainly on cardiac and respiratory diseases. The best treatment is prevention through genetic counseling and antenatal diagnosis. OBSERVATIONS We report three cases of CHARGE syndrome treated in our department. It was about two males and one female. The diagnosis was at birth in two cases with bilateral choanal atresia and at the age of six years in one case with unilateral atresia and a contralateral stenosis. The diagnosis of CHARGE syndrome was deducted from a set of clinical arguments (Table I). This diagnosis was made by pediatricians after series of investigations including facial CT scan, echocardiography, abdominal ultrasound and an intravenous urography when associated with urinary symptoms. Table I : Clinical history of the three cases of CHARGE syndrome Corresponding Author : Rym BECHRAOUI adress: rbechraoui@yahoo.fr 68 J. TUN ORL - N 40 DECEMBRE 2018

2 R. Bechraoui and al SYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME Figure 1 : Bilateral bone choanal atresia Figure 4 : Complete choanal atresia on the right side. Choanal stenosis on the left side We did not notice any life-threatening malformation associated to choanal atresia. CTscan allowed differentiating between a bony or membranous choanal atresia. An urgent management was required because of a bilateral choanal atresia in two cases leading to a neonatal respiratory distress. It consisted of intubation then trans-nasal puncture using a of small-caliber plastic catheter.secondly, choanal atresia unblocking was conducted through trans-palatal approach in one case and through endoscopic approach in the remaing two cases. Functional outcome was satisfactory with re-stenosis of one choana in only one patient (Table II). Figure 2 : Major aplasia of the ear Table II : Clinical history of the three cases of CHARGE syndrome Figure 3 : Malformation of the right internal ear with Mondini defect J. TUN ORL - N 40 DECEMBRE

3 SYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME R. Bechraoui and al DISCUSSION CHARGE syndrome is a rare but serious genetic disease [1]. The real incidence of this syndrome is not known;with estimates ranging from 0.1 to 1.2/10000 live births [3]. In 1979, this syndrome was described by both Hall and Hittner in children with multiple congenital anomalies that were observed for choanal atresia and coloboma. In 1981, Pagon and colleagues, first invented the acronym CHARGE association (Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) [1,4]. So that, the diagnosis of the CHARGE association is mainly clinical [1,2,5,6]. More recently,in 1998, an expert group of geneticists and developmental pediatricians defined the major (the classical 4 C s: Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) and minor criteria of CHARGE syndrome [3]. Major criteria are those findings that occur commonly in CHARGE syndrome but are relatively rare in other conditions (Table N II). Minor criteria occur less frequently or are less specific of CHARGE syndrome (Table II, table III) [1-3,5,6]. Patients are at a high risk to have CHARGE syndrome if are present: - All four major characteristics (Choanal atresia, Coloboma, Characteristic ears and Cranial nerve anomalies) or [1-3,5] - Three major characteristics (one being either choanal atresia or coloboma) and three minor characteristics are highly likely [3,4]. All the malformations in CHARGE syndrome occur early in embryogenosis, during the 4th and 5th weeks after conception [3,6]. Genetic mutations have been found in more than half of children with this syndrome [7]. These mutations were located in a member of the chromodomain gene family CHD7 [3]. In most cases, the mutation was de novo [3,5,7].However, genotype-phenotype predictions remain yet imprecise [3]. Most cases of CHARGE syndrome are sporadic[3,6]. Though, autosomal dominant, autosomal recessive, and X-linked recessive inheritance have been suggested in few familial cases [6].So that,all children or adults suspected with CHARGE syndrome should have a formal evaluation by a medical geneticist and a genetic counseling [1,3,5,7]. Most of the abnormalities associated with CHARGE syndrome are difficult to diagnose antenatally using sonography unless there is a high suspicion with the presence of hydramnios. Arhinencephaly and semicircular canal agenesis were the two constant features in fetuses with CHARGE syndrome and CHD7 mutations [3]. All patients suspected of having CHARGE syndrome should have a cardiology consultation and a complete eye examination by an ophthalmologist. Hearing aids should be used as soon as hearing loss is documented.cochlear implantations have been successfully performed in patients with CHARGE association[3,8]. For endocrine problems, sex steroid therapy has been used for the descent of testesin males suffering from this syndrome [3]. Children with CHARGE syndrome require intensive medical care as well as multiple surgical interventions. The most common emergency in neonates with CHARGE syndrome involves cyanosis due to bilateral choanal atresia and/or congenital heart defects. The primary aim of management should be airway stabilization and circulatory support [3,4]. Choanal atresia is manifested by narrowing and closure of the posterior choanae of the nose. It can be either a blockage (choanal atresia) or a narrowing (choanal stenosis). It can affect the two sides (bilateral) or only one side (unilateral). There may be bony or membranous obstruction or mixed one [4]. There may also be associated with abnormalities of the skull base (such as thickenedatretic plates or defects in the skull base) which may make surgery more challenging [4]. About one half of patients presenting with choanal atresia have other associated anomalies or syndromes such as CHARGE (7 to 29%), Treacher Collins, Crouzon, Pfeiffer, Antley Bixler, Marshall Smithand Schinzel Giedion syndromes [4,9]. The usual presentation of bilateral choanal atresia is obvious, manifesting as airway obstruction, stridor and paradoxical cyanosis (infants turn pink when crying as they begin to breathe through an open mouth). A temporizing measure, such as an oral airway, McGovern nipple, or intubation is often required prior to definitive surgical treatment [4,6,10].When it is unilateral,choanal atresia typically present later (usually 5-24 months) as unilateral obstruction and persistent nasal discharge. Diagnosis can rarely be delayed to adulthood [4]. 70 J. TUN ORL - N 40 DECEMBRE 2018

4 R. Bechraoui and al SYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME Table II : Major criteria for the Diagnosis of CHARGE syndrome Table III : Minor criteria for the Diagnosis of CHARGE syndrome J. TUN ORL - N 40 DECEMBRE

5 SYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME R. Bechraoui and al CONCLUSION CHARGE syndrome is considered as a highly complex medical condition requiring a significant consumption of health care,especially during the first year of life, as well as a considerable amount of different health care contacts. This is a serious disease and the overall outcome and survival may be improved only if there is good collaboration between specialists of different fields. Conflicts of interest: Authors declared no conflicts of interest. REFERENCES 1. Onaran Z, Yimazbas P, Ornek K. Bilateral punctum atresia and lacrimal sac fistula in a child with CHARGE syndrome. Clinical & experimental ophthalmology. 2009;37: Lobete Prieto CJ, Llano Rivas I, Fernandez Toral J, Madero Barrajon P. CHARGE syndrome. Archivos argentinos de pediatria. 2010;108:e9-e Blake KD, Prasad C. CHARGE syndrome. Orphanet journal of rare diseases. 2006;1: Ramsden JD, Campisi P, Forte V. Choanal atresia and choanal stenosis. Otolaryngologic clinics of North America. 2009;42: , x. 5. Hall BD. Choanal atresia and associated multiple anomalies. The Journal of pediatrics. 1979;95: Hsueh KF, Yang CS, Lu JH, Hsu WM. Clinical characteristics of CHARGE syndrome. Journal of the Chinese Medical Association : JCMA. 2004;67: Michelucci A, Ghirri P, Iacopetti P, et al. Identification of three novel mutations in the CHD7 gene in patients with clinical signs of typical or atypical CHARGE syndrome. Inter J Pediatr Otorhinolaryngol. 2010;74: Birman CS, Brew JA, Gibson WP, Elliott EJ. CHARGE syndrome and Cochlear implantation: difficulties and outcomes in the paediatric population. Inter J Pediatr Otorhinolaryngol. 2015;79: Riepl R, Scheithauer M, Hoffmann TK, Rotter N. Transnasal endoscopic treatment of bilateral choanal atresia in newborns using balloon dilatation: own results and review of literature. Inter J Pediatr Otorhinolaryngol. 2014;78: Tadmor R, Ravid M, Millet D, Leventon G. Computed tomographic demonstration of choanal atresia. AJNR. Am J Neuroradiol. 1984;5: Effat KG. Use of the automatic tympanometer as a screening tool for congenital choanal atresia. The Journal of laryngology and otology. 2005;119: De Freitas RP, Berkowitz RG. Bilateral choanal atresia repair in neonates--a single surgeon experience. Inter J Pediatr Otorhinolaryngol. 2012;76: Uzomefuna V, Glynn F, Al-Omari B, Hone S, Russell J. Transnasal endoscopic repair of choanal atresia in a tertiary care centre: a review of outcomes. Inter J Pediatr Otorhinolaryngol. 2012;76: Kubba H, Bennett A, Bailey CM. An update on choanal atresia surgery at Great Ormond Street Hospital for Children: preliminary results with Mitomycin C and the KTP laser. Inter J Pediatr Otorhinolaryngol. 2004;68: Teissier N, Kaguelidou F, Couloigner V, Francois M, Van Den Abbeele T. Predictive factors for success after transnasal endoscopic treatment of choanal atresia. Archives of otolaryngology--head & neck surgery. 2008;134: Al-Ammar AY. Effect of use of mitomycin C on the outcome of Choanal atresia repair. Saudi medical journal. 2007;28: Holland BW, McGuirt WF, Jr. Surgical management of choanal atresia: improved outcome using mitomycin. Arch Otolaryngol Head & Neck Surg. 2001;127: Rombaux P, de Toeuf C, Hamoir M, Eloy P, Bertrand B, Veykemans F. Transnasal repair of unilateral choanal atresia. Rhinology. 2003;41: Eladl HM. Transnasal endoscopic repair of bilateral congenital choanal atresia: controversies. Journal Laryngol Otol. 2010;124: Hengerer AS, Brickman TM, Jeyakumar A. Choanal atresia: embryologic analysis and evolution of treatment, a 30-year experience. The Laryngoscope. 2008;118: Pasquini E, Sciarretta V, Saggese D, Cantaroni C, Macri G, Farneti G. Endoscopic treatment of congenital choanal atresia. Inter J Pediatr Otorhinolaryngol. 2003;67: Ibrahim AA, Magdy EA, Hassab MH. Endoscopic choanoplasty without stenting for congenital choanal atresia repair. Inter J Pediatr Otorhinolaryngol. 2010;74: Agrawal N, Morrison GA. Laryngeal cancer after topical mitomycin C application. Journal Laryngol Otol. 2006;120: J. TUN ORL - N 40 DECEMBRE 2018