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INTRODUCTION ––––––––––––––––––––––––First described in 1979 by Hall and Hittner et al, CHARGE syndrome was initially defined as a non-random associa-tion 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 dia-gnoses 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 uni-lateral 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 pediatri-

cians after series of investigations including facial CT scan, echocardiography, abdominal ultrasound and an intrave-nous urography when associated with urinary symptoms.

Table I : Clinical history of the three cases of CHARGEsyndrome

C A S E R E P O R T———————————————————————————————————————————————————————

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.

Corresponding Author : Rym BECHRAOUIE-mail adress: rbechraoui@yahoo.fr

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R. Bechraoui and al SYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME

Figure 1 : Bilateral bone choanal atresia

Figure 2 : Major aplasia of the ear

Figure 3 : Malformation of the right internal ear with Mondini defect

Figure 4 : Complete choanal atresia on the right side. Choanal stenosis on the left side

We did not notice any life-threatening malformation asso-ciated 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 respi-ratory distress. It consisted of intubation then trans-nasal puncture using a of small-caliber plastic catheter.Se-condly, choanal atresia unblocking was conducted through trans-palatal approach in one case and through endosco-pic approach in the remaing two cases. Functional outcome was satisfactory with re-stenosis of one choana in only one patient (Table II).

Table II : Clinical history of the three cases of CHARGEsyndrome

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R. Bechraoui and alSYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME

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, Re-tarded 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 re-cently,in 1998, an expert group of geneticists and develop-mental pediatricians defined the major (the classical 4 C’s: Choanal atresia, Coloboma, Characteristic ears and Cra-nial nerve anomalies) and minor criteria of CHARGE syn-drome [3]. Major criteria are those findings that occur com-monly 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 ear-ly 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 re-main 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 syn-

drome are difficult to diagnose antenatally using sonogra-phy unless there is a high suspicion with the presence of hydramnios. Arhinencephaly and semicircular canal agene-sis 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 im-plantations have been successfully performed in patients with CHARGE association[3,8]. For endocrine problems, sex steroid therapy has been used for the descent of teste-sin males suffering from this syndrome [3].Children with CHARGE syndrome require intensive medi-cal 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 bloc-kage (choanal atresia) or a narrowing (choanal stenosis). It can affect the two sides (bilateral) or only one side (uni-lateral). There may be bony or membranous obstruction or mixed one [4]. There may also be associated with abnor-malities 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 syn-dromes [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 tempori-zing measure, such as an oral airway, McGovern nipple, or intubation is often required prior to definitive surgical treat-ment [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 de-layed to adulthood [4].

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SYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROMER. Bechraoui and al

Table II : Major criteria for the Diagnosis of CHARGE syndrome

Table III : Minor criteria for the Diagnosis of CHARGE syndrome

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R. Bechraoui and alSYNDROMIC CHOANAL ATRESIA: THE EXAMPLE OF CHARGE SYNDROME

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 sur-vival may be improved only if there is good collaboration between specialists of different fields.

Conflicts of interest: Authors declared no conflicts of in-terest.

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