Archives ofDisease in Childhood 1990; 65: 217-223 217 Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from Who's in CHARGE? Multidisciplinary management of patients with CHARGE association

K D Blake, I M Russell-Eggitt, D W Morgan, J M Ratcliffe, R K H Wyse

Abstract that patients should exhibit at least four of the Clinical experience of 50 patients with the major abnormalities listed by Pagon et al.2 CHARGE association is reviewed and prob- Detailed information on the precise range of lems with management of children born with abnormalities presented by each patient as well multiple system involvement is highlighted. It as their medical and surgical management was was found that the outlook for survival was stored on an Amdahl mainframe computer. poor if more than one of the following three Data was analysed using an SAS statistical features was present: cyanotic cardiac package and employing X2 and Kaplan-Meier lesions, bilateral posterior choanal atresia, or actuarial survival analysis as appropriate. tracheo-oesophageal fistula. Mortality was largely due not to the structural heart defects or choanal abnormalities, but reflected under- Results lying pharyngeal and laryngeal incoordina- ACTUARIAL SURVIVAL ANALYSIS tion, which resulted in aspiration of secre- Of the 50 patients with CHARGE association, tions. Outcome is likely to be improved if col- 13 have died (nine boys and four girls). laboration between specialist surgical teams Actuarial survival analysis (fig 1) was 70% at allows necessary procedures to be performed five years and showed that, of those who died, using the minimum number of anaesthetics. most succumbed in the first year of life. Three Examination of both the short and long term patients died as neonates, seven died between management of these children has stressed 1 month and 1 year of age, and three died the importance of a multidisciplinary between 1 and 5 years of age. Seven of these 13 approach to their care. patients (54%) died of aspiration. Considering that a further five patients had either with- drawal of support or sudden death (cause CHARGE association was first described by unknown), aspiration of secretions may clearly Hall et al in 1979,' but the acronym CHARGE represent the major incremental risk factor (Colobomata, Heart defect, choanal Atresia, (table 1). http://adc.bmj.com/ growth and/or developmental Retardation, Genital hypoplasia, Ear abnormalities) was initially coined by Pagon et al in 1981.2 Since SURGICAL MANAGEMENT then it has become clear that facial palsy, renal Thirty two patients presented with , abnormalities, orofacial clefts, and oesophageal which was due to congenital heart disease in 12, atresia frequently accompany the main choanal atresia in 12, and to a combination of features.3 4Despite extensive description of the heart disease and choanal atresia in eight. on September 24, 2021 by guest. Protected copyright. features that comprise the CHARGE acronym, there have been virtually no reports of the man- agement, outcome, and survival of these 100- Department of patients. As the number of patients with Paediatric Cardiology, CHARGE association who have attended this Institute of 80- Child Health, hospital far exceeds any published series, we felt 21 10 3 Survival London it appropriate to describe our K D Blake multidisciplinary R K H Wyse experience in the clinical management of these 4c 60- Hospital for patients. We also felt it important to consider, Sick Children, from all the clinical specialities that inevitably London, become involved in the management of these Ophthalmology O 40- Department patients, which team should be in charge of I M Russell-Eggitt organising long term care? 12 Ear, Nose, and 20- 6 Throat Department First surgery D W Morgan Patients and methods

Respiratory Unit The study comprised 50 patients with 0J I I J M Ratcliffe CHARGE association; 29 were boys and 21 0 2 4 6 8 10 12 14 16 18 Correspondence to: were girls. All patients were referred from Years Dr R K H Wyse, Department of district general hospitals to one of the following Figure I Upper curve: Kaplan-Meier actuarial survival of Paediatric Cardiology, departments within this institution: cardiology, 50patients with CHARGE association. Numbers along the Institute of Child Health, curveportray how many patients were still beingfollowed up. 30 Guilford Street, respiratory medicine, gastroenterology, ear, Lower curve: actuarial analysis ofthe time elapsed before London WC1 IEH. nose, and throat, ophthalmology, and genetics. each patient with CHARGE association required theirfirst Accepted 11 September 1989 The criteria for inclusion in this study required surgicalprocedure. 218 Blake, Russell-Eggitt, Morgan, Ratcliffe, Wyse

Table I Details of The actuarial probability of patients with Table 3 Outcome

children who died (n=13) Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from CHARGE association requiring at least one Abnormality Total Alive Dead % No of major surgical intervention is shown in fig 1. or risk No Mortality patients Twenty six patients (52%) required surgery as factor Died< 1 month neonates (table 2). By 1 year of age nearly three Bilateral choanal atresia 16 9 7 44 postoperatively 7* quarters of the patients had undergone some Cyanotic heart disease Died of aspiration presenting in first week 21 10 11 52 pneumonia 2 form of major surgery and a further five have Bilateral choanal atresia Decision to adopt no needed a general anaesthetic for 'minor' and cyanotic heart active treatment 1 disease 7 1 6 86 Sudden death: cause procedures. Tracheo-oesophageal unknown 3 atresia and fistula 5 2 3 60 The 50 patients in the study have so far Tracheo-oesophageal *These seven children died required 114 major surgical procedures (aver- fistula and bilateral from aspiration (n=5), dis- age: 2-3/patient). Patients with bilateral post- choanal atresia 2 0 2 100 seminated intravascular coa- Tracheo-oesophageal gulation from sepsis (n= 1), erior choanal atresia received proportionally fistula and cyanotic heart and withdrawal of treatment disease 4 1 3 75 more surgical procedures (2-8/patient) and Given prostagladin E2 8 1 7 87 (n= 1). investigations under general anaesthetic (4 7/ Tracheostomy 7 4 3 43 patient) than the remainder who required only 1-6 surgical procedures/patient and 3-3 investigations/patient. Only two patients have not required any CONGENITAL HEART DISEASE surgery; in contrast, two patients have needed Congenital heart disease was present in 42 eight major operations. Although reoperations (84%) patients; the other eight had normal were predominantly for choanal dilatation, hearts. The range of cardiac malformations cardiac repair, or insertion of grommets, a varied but there was a preponderance of right number of patients required genitourinary, sided lesions. Thirty patients had major con- ophthalmic, or plastic surgery. Six patients genital heart disease (defined as requiring underwent repair of cleft palate, three patients surgery) (table 4), six ofwhom also had aberrant had operations for skeletal abnormalities, one subclavian arteries. needed aspiration of a cerebral abcess, and Patent ductus arteriosus was associated with another required excision of occipital encepha- severe cardiac lesions in 19 patients: 13 were locele. large enough to require surgical closure, five Furthermore, there were 12 Nissen fundopli- closed spontaneously, and in one patient, who cation operations for gastro-oesophageal reflux subsequently died, it was not treated at the or formation of a feeding gastrostomy and seven request of the parents. patients needed a tracheostomy. Four patients Twelve patients had (haemodynamically) required both operations and, although these comparatively mild heart defects: either a small four may have been expected to have the most atrial or ventricular septal defect, pulmonary severe defects, none of them had bilateral post- stenosis, patent ductus arteriosus, or a combina- erior choanal atresia. tion of these. Half of the children who survived more than http://adc.bmj.com/ one year had needed at least one operation for myringotomies, a third required microlaryn- RESPIRATORY PROBLEMS gobronchoscopy (average of two repeats/ Twenty eight (56%) patients had choanal atresia patient), a quarter needed some form of eye or stenosis and 19 (38%) had no defect; three surgery, and nearly a quarter of the boys had were not examined. orchidopexy. Sixteen patients had bilateral posterior

We found that patients with CHARGE choanal atresia (BPCA), and a high proportion on September 24, 2021 by guest. Protected copyright. association had a high postoperative mortality. of these (nine of 16, 56%) also had facial palsy. There was no correlation with the type of surgery, but of those who died all had at least three general anaesthetics before death, includ- Table 4 Range of congenital heart disease in patients ing one patient who had 12. requiring cardiothoracic surgery (n=30) It was not possible by retrospective analysis to predict with certainty those patients who No ofpatients represented a high operative risk (table 1) but Tetralogy of Fallot 4 Fallot with AVSD 4 certain combinations of features seemed to pre- Failot with Ebstein's anomaly 1 dispose to a poor outcome, particularly bilateral AVSD alone 2 AVSD with DORV 1 posterior choanal atresia combined either with AVSD with TAPVC 1 cyanotic heart disease or trahceo-oesophageal Pulmonary atresia/VSD 2 DILV with SRAVV and pulmonary stenosis 1 fistula (table 3). DORV with pulmonary stenosis and VSD 1 Pulmonary stenosis with aortic stenosis 1 Pulmonary stenosis and secundum ASD 1 TGA with pulmonary stenosis 1 VSD and PDA 2 Table 2 Details of neonatal surgery (n=26) VSD and secundum ASD 2 VSD with Ebstein's anomaly 1 No of patients VSD 2 Secundum ASD and PDA 2 Choanal atresia repair 10 Coarctation of the aorta and PDA 1 Tracheo-oesophageal fistula 5 Cardiac surgery 7* ASD, atrial septal defect; AVSD, atrioventricular septal defect; Tracheostomy 2 DILV, double inlet left ventricle; DORV, double outlet right Inguinal hernia I ventricle; PDA, patent ductus arteriosus; SRAVV, straddling Cutback for imperforate anus 1 right atrioventricular valve; TAPVC, total anomalous pulmonary venous connection; TGA, transposition of great *Four were palliative. arteries; and VSD, ventricular septal defect. Who's in CHARGE? Multidisciplinary management ofpatients with CHARGE association 219

Ten children with BPCA were alive at 18 Microphthalmos (considered to be part of the

months of age, all had severe feeding problems 'typical ' spectrum in that the defect Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from and exhibited a pronounced failure to thrive. arises from incomplete apposition of the fetal They all required grommets, and all showed fissure of the optic cup) was present in 22 of the more severe developmental retardation than the 50 patients: it was bilateral in nine, right sided children without BPCA. Of these 10 survivors, in six, and left sided in seven. However, it was eight had inner ear problems ranging from predominantly mild with only two patients hav- severe sensorineural deafness to structural ing eyes that offered no useful vision. temporal defects, eight had gastro- Nystagmus was present in 13 patients with oesophageal reflux of whom two required visual acuity ranging from 6/9 to 'bare naviga- Nissen's fundoplication, four had laryngeal tion'. Strabismus was detected in 16 patients problems, and three needed a tracheostomy. (seven divergent, six convergent, and three vari- Children with BPCA required more operations able). Refractive errors were common (myopia, and investigations than the other CHARGE hypermetropia, and astigmatism), and in eight patients and, as a consequence, they spent sub- patients there was more than two dioptres of stantially more time in hospital. In contrast, anisometropia. Spectacles have improved visual none of the nine patients who had either performance in 10 patients. unilateral choanal atresia or stenosis died and Despite copious lubrication and lateral only two of them required grommets. tarsorrhaphy, three patients with facial palsy Polyhyramnios can be a predictor for BPCA; had corneal scarring. of the eight children born to mothers with Retinal detachment as a complication of polyhydramnios, seven had BPCA. colobomata occurred bilaterally in two patients and, at the time of diagnosis, one eye in each EAR ABNORMALITIES case was already inoperable. Both of the fellow All 50 patients had abnormal pinnae or deaf- eyes have required vitreoretinal surgery with ness, or both. Most patients (94%) had the removal of the lens and silicone oil exchange typical external features of lop or cup shaped with useful vision presently retained. ears with a minority being low set only. In 34 (68%) the ear abnormalities were bilateral. Two thirds of the patients had middle ear GENITAL AND ENDOCRINE ABNORMALITIES problems, consisting of ossicular malforma- Of the 29 male patients, 28 (96%) had external tions, stapedius tendon abnormalities or chronic genital abnormalities including at least 25 (86%) serous otitis media, or both, resulting in con- with micropenis (two were not documented); 17 ductive hearing loss. (58%) had bilateral undescended testis. Of 21 Nineteen (38%) suffered inner ear abnormali- male patients over 1 year of age, 15 had growth ties of the cochlear or semicircular canals result- retardation and cryptorchidism, two had ing in severe sensorineural growth above the 3rd centile and cryptor- deafness, and 15 chidism, four had normal (30%) had severe mixed all growth and http://adc.bmj.com/ hearing loss; descended testes. Full endocrine assessments required hearing aids. have not been completed on all the older chil- Eight patients had cleft lip or palate, or both, dren in our study; however, one boy was found and four of these had evidence of glue ears. Of to be growth hormone deficient. Four of the the 28 children with choanal atresia or stenosis, boys over 9 years old were studied for gonado- 22 (78%) had bilateral external ear abnormali- trophin deficiency and all were found to have ties. flat luteinising hormone releasing hormone responses and negligible testosterone rise to on September 24, 2021 by guest. Protected copyright. OCULAR MANIFESTATIONS human chorionic gonadotrophin. Coloboma affecting either one or both eyes was detected in 43 patients of the 47 examined by an ophthalmologist. Of these, only 16 had iris OTHER ASSOCIATED FEATURES coloboma (two of these 16 had partial defects Renal abnormalities (malrotation, hydro- shown on transillumination of the iris). Two nephrosis, reflux) were present in 12 (24%) patients had normal fundi with iris coloboma, patients. Thirteen (26%) patients had laryngeal but 28 patients had fundal colobomata with malformations (, laryngeal clefts, normal irides. There was one case of eyelid abnormal aryepiglottic folds). Forty four (88%) colobomata, which has not previously been had feeding problems and, of these, 20 (45%) reported in patients with CHARGE association. had gastro-oesophageal reflux. Five patients Colobomata affected the posterior segment in (11%) had oesophageal atresia with tracheo- 38 of the 50 patients, this was bilateral in 32 oesophageal fistula. patients, and in all except nine eyes (in five Skeletal abnormalities were present in 20 patients) the optic disc was involved. Quantita- (40%) patients. Eleven patients had hemiverte- tive assessment of vision has been possible in 13 brae or scoliosis; nine had abnormalities of the patients; we found acuity of eyes with disc extremities, predominantly syndactyly or coloboma varied from Snellen 6/9 to bare light clinodactyly. perception. One patient had a retinochoroidal coloboma without optic disc involvement and vision was 6/5. Segmental hypoplasia of the GROWTH RETARDATION optic nerve head was reported in four eyes (in all Eleven neonates (22%) had intrauterine growth cases it was the patient's better eye) and their retardation and all subsequently continued to be acuity ranged from 6/6 to 6/18. growth retarded. However, not all children with 220 Blake, Russell-Eggitt, Morgan, Ratcliffe, Wyse

Table S Details of patients over I year of age (n=34) mal findings on electroencephalography. The

Failure to Relatively normal association between abnormal neurological find- Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from thrive: height growth: height and ings, hypotonia, and facial palsy is shown in and weight weight >3rd centile 6. A <3rd centile (n=8) table number of patients were reported by (n=26) their parents to have infantile spasms in the Feeding difficulties 24 4 absence of any fever.5 Gastro-oesophageal reflux 15 1 Nissen's fundoplication 6 0 Larynx/pharynx problems 8 0 Facial palsy 15* 1* Discussion No of major operations Management of patients with CHARGE asso- (minimum/maximum) 1/5 0/1 Average/patient 1-4 0-5 ciation is a challenging task both for the general paediatrician and other teams. Inte- *Of the children with facial palsy and failure to thrive, all 15 had specialist feeding difficulties and 10 gastro-oesophageal reflux; the one grated management is vital if these children are child with relatively normal growth had both feeding difficulties to reach their full potential. and gastro-oesophageal reflux. In our attempt to ascertain from hospital records a complete list of patients with postnatal growth retardation had poor intra- CHARGE association, we found a surprisingly uterine growth. In the first year of life, 39 high number of children with two or three of patients had growth retardation (defined here as the main features who could not be categorised weight falling to below the 3rd centile), four as having CHARGE association under the patients were not growth retarded, five died at current nomenclature yet clearly appeared to be less than 2 months of age, and two were too of the same broad phenotype. They also exhi- young for assessment. Of the 34 children over 1 bited many of the associated anomalies found in year old, 26 (76%) had growth retardation and CHARGE association such as those involving eight (24%) were on or above the 3rd centiles. the vertebra, kidneys, facial palsy, short neck, Data relating to the clinical management of hypertelorism, and widely spaced nipples. these 34 patients is presented in table 5. Diagnosis, although straightforward in patients with all six of the main features of CHARGE, can become more difficult in several DEVELOPMENTAL DELAY ways. First, diagnosis of CHARGE association Twenty six patients (52%) with CHARGE asso- in a neonatal girl may be more difficult than in a ciation had developmental delay; eight (17%) boy because abnormalities of external genitalia did not. Sixteen were too young for assessment. do not occur. Therefore only five of the criteria Of those with normal developmental none had for CHARGE are available, and growth retarda- BPCA. Of the eight children with normal tion may not yet be apparent. This is where the development, seven had either colobomata or other associated abnormalities, particularly auditory problems but not both. facial palsy, may be of value in the initial A variety of neurological signs were noted in diagnosis. Second, difficulties of diagnosis may these patients. Facial palsy was observed at or also be encountered with a neonatal boy who http://adc.bmj.com/ soon after birth in 21 patients (right in 12, left in has coloboma, micropenis, and low set ears but seven, with two bilateral). Most palsies were no heart defect or choanal atresia. A final congenital with only three being acquired. Nine diagnosis of CHARGE association would patients had microcephaly (defined here as a require specific subsequent confirmation of head circumference below the 3rd centile when developmental retardation especially as none of measured at birth). Of these nine, all had his lesions in themselves would affect childhood

developmental delay but the converse was not development. For most cases, however, the on September 24, 2021 by guest. Protected copyright. found. We found no correlation between the typical facial appearance (fig 2) of lop/cup shape severity of mental retardation and the presence protruding ears and facial asymmetry should be of microcephaly. Eleven patients (22%) had enough to alert the general paediatrician abnormalities shown on computed tomography: especially if there is cyanosis or respiratory dis- eight had mild atrophy, one had an occipital tress in the newborn. Most cases of CHARGE encephalocele, one had agenesis of the corpus association have been sporadic but in some callosum, and one had communicating hydro- there is clearly a genetic component2 19 with cephalus. Fourteen patients (28%) had abnor- both autosomal dominantl' and recessive" transmission having been reported. Although karyotypic analysis is generally reported as nor- mal in these patients, it is important to identify Table 6 Association between abnormal neurological any chromosomal abnormalities before making findings, hypotonia, and facial palsy a diagnosis of CHARGE association as a variety Hypotonia Facial palsy Hypotonia of chromosomal abnormalities can occur in and facial palsy association with colobomata and choanal atresia. In view of the overlap between Abnormal computed tomogram (n=ll) 6 5 4 CHARGE association and the DiGeorge Abnormal electro- sequence, it is important to confirm the integ- encephalogram (n=14) 11 8 7 Abnormal computed rity of chromosome 22 and to evaluate for tomogram and thymic and parathyroid dysfunction.'2 electroencephalo- gram (n=7) 6 5 5 For optimal management, the patient with Deaths (n=13) 5* 6 1 CHARGE association should ideally be referred *Of the eight children without hypotonia who died, two were to a hospital that can undertake all areas of hypertonic, three had unknown tone, and three normal tone. specialist treatment and management. This Who's in CHARGE? Multidisciplinary management ofpatients with CHARGE association 221

As in previous reports, however, conotruncal defects were prominent.'5 For a blue neonate presenting at a referring Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from hospital, once an oral airway is established and the child remains cyanosed the cause is likely to be cyanotic congenital heart disease. The infant should be stabilised and transported to a regional referral centre. Neonates who were given prostaglandin E2, Figure 2 Typical usually at the referring hospital for cyanotic appearance ofCHARGE heart disease, had a high mortality (table 3). association, particularly This poor outcome may reflect the fact that apparent are the low set, these patients were critically ill neonates. It was dysmorphic ears andfacial asymmetry. subsequently shown that three of these patients had high pulmonary blood flow, however, and in retrospect they should not have received prostaglandin during transfer. Conversely, some patients with restrictive pulmonary blood flow survived transfer without receiving pros- taglandin. Patients with CHARGE association may require an early shunt procedure before a later definitive repair. It may be possible to send patients directly for cardiac surgery on the basis of echocardiographic findings alone; however, cardiac catheterisation may be necessary to identify anomalous subclavian vessels or to rule helps in long term follow up, benefits the out peripheral pulmonary stenosis, or both. parents, and most importantly it offers an In our experience, parents may decline treat- integrated, multidisciplinary approach. In this ment if their child has multiple defects, even if way surgical management can unify with in our opinion their child is likely to survive investigations that also require a general their cardiac surgery. anaesthetic. This requires active coordination and cooperation between the appropriate specialities. In our series of patients it is prob- MANAGEMENT OF CHOANAL ATRESIA able that a more unified multidisciplinary Bilateral posterior choanal atresia is an approach could have reduced the number of uncommon congenital abnormality with an inci- general anaesthetics by at least 25% and this dence of one in 5000-8000 live births and may to have helped reduced morbidity and presentation is with cyclical cyanosis relieved by http://adc.bmj.com/ possibly mortality. High postoperative mortal- crying. If choanal atresia is unilateral, persistent ity may reflect the laryngopharyngeal incoordi- nasal discharge occurs. Anatomically there is nation, which can be present even when there is failure to develop patency between the nasal no structural anomaly. Over half of the deaths cavity and nasopharynx, which occurs between in our series of patients were attributable to the 25th to the 45th day of embryonic life. aspiration of secretions. It is clearly important Once the diagnosis of choanal atresia has been to be aware of this risk when considering the confirmed, stabilisation of the neonate by oral postoperative management and to realise that airway should be followed by urgent transfer to on September 24, 2021 by guest. Protected copyright. most of these patients have complications after a regional centre. Computed tomography has anaesthesia. The respiratory problems encoun- emerged as the diagnostic radiological proce- tered in CHARGE association are secondary to dure of choice in evaluating posterior choanal the oro/nasopharyngeal, oesophageal, and atresia.'6 It gives the surgeon detailed anato- cardiac manifestations. The most severely mical information about the type of atresia or affected group were unable adequately to stenosis-that is, bony or membranous, uni- swallow their secretions. They required lateral or bilateral-and this clearly may influ- tracheostomies to avoid recurrent aspiration of ence the choice of surgical approach in repair of secretions and, after this procedure, needed the lesion. In our experience the transnasal very frequent suction for a prolonged period of repair is far more satisfactory than the trans- time. palatal approach. Nasal stents are usually required for six weeks and patients may require further dilatations to guarantee nasal patency. It CARDIOLOGICAL EVALUATION is suggested that any child with abnormalities of We found that heart disease tended to be severe the choanae has investigations for associated in CHARGE association. Tetralogy of Fallot structural problems in other systems.'7 As we and atrioventricular septal defects were the found a close association between BPCA and most common cyanotic cardiac defects in our chronic serous otitis media one could argue a group of patients and, as reported previously, strong case for prophylactic grommets. patent ductus arteriosus was a common finding It should be possible to scan the temporal either alone or associated with more severe and brain at the same time and so prevent lesions.'3 We did not find the high incidence of a repetition of general anaesthesia for each of aortic arch anomalies cited by other authors.'4 these procedures. There should be prompt 222 Blake, Russell-Eggitt, Morgan, Ratcliffe, Wyse

investigation for possible cardiac anomalies or association easier in boys. There has been a tracheo-oesophageal atresia as either of these report of labial hypoplasia in two females over major defects, especially when associated with 15 years old but similar findings were not estab- Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from choanal atresia, carry a high risk of mortality lished in our series of 21 girls. (fig 1 and table 3). This attrition may be, in There appeared to be a direct association part, due to the fact that these children need a between growth retardation in the boys and number of general anaesthetics very early in bilateral undescended testis. This may be a con- life. sequence of more pronounced hypothalamic hypopituitarism in the group with cryptor- chidism. Of those tested, however, growth EAR ABNORMALITIES hormone deficiency was only found in one The initial assessment consists of examination patient. Follicle stimulating hormone and of the tympanic membranes to exclude a middle luteinising hormone deficiencies were found in ear effusion. Then brain stem evoked three of our patients, but most have not had full audiometry may be used to help assess the level assessments. Hypothalamic dysfunction has of hearing, and computed tomography of the been suggested as a cause of the temporal bone is used to exclude ossicular or hypopituitarism,3 18 whereas other reports have inner ear abnormalities. described high concentrations of follicle stimu- The insertion of grommets for chronic serous lating hormone and low baseline testosterone otitis media may make an enormous difference concentrations indicating a primary gonadal to the quality of life, and needs to be under- dysfunction.'9 Treatment for these particular taken early as the first two years of life are problems is not universally accepted but vitally important in the development of speech. administration of low dose androgens for a Chronic serous otitis media was very common in limited time has enhanced penile growth.20 patients with CHARGE association, and many It is important to look specifically for struc- required early myringotomies with insertion of tural kidney abnormalities that can be associ- grommets, which resulted in rapid improve- ated with reflux. We found that facial palsy was ment in language development and balance. often present in patients with renal problems Often three or four repeat procedures were and the lesions tended to be on the same side of necessary when they were older at a time when the body. one would expect middle ear effusions to have disappeared. It is also important to recognise that, even in the presence of structural GROWTH RETARDATION anomalies or sensorineural deafness, alleviating Feeding difficulties were a major feature in glue ear can be beneficial. Assessment by an patients who failed to thrive. The diagnosis of audiological physician and the prescribing of gastro-oesophageal reflux was made by barium hearing aids for the more severely deaf is essen- swallow but the inert nature of barium sulphate tial. Involvement of the peripatetic teacher of may underestimate the number of patients with

the deaf at an early age will allow counselling for reflux. Therefore pH study techniques would http://adc.bmj.com/ parents and offer better provision for educa- be more appropriate in patients with feeding tional needs. difficulties. Pharyngeal incoordination was pre- sent in 14 of our patients and, in those who underwent microlaryngobroncoscopy, struc- OPHTHALMOLOGICAL REVIEW tural defects were often found (that is, clefts of An initial examination by an ophthalmologist the larynx or pharynx, short aryepiglottic folds, may show an important ocular defect, alter- and laryngomalacia). Many mothers expressed natively it may detect a subtle coloboma with difficulty in weaning the children to any form of on September 24, 2021 by guest. Protected copyright. little relevance to ocular morbidity, but will aid lumpy solid food. Our findings indicate that the diagnosis of the CHARGE association. facial palsy was associated with feeding prob- Anisometropia (a difference in refraction of lems or gastroesophageal reflux, or both, and more than two dioptres between eyes) and could therefore be used as a useful predictor for strabismus are both causes of amblyopia, which these and also for failure to thrive. are potentially amenable to occlusion treatment. Regular six monthly review is advised for the children with structural abnormalities as com- DEVELOPMENTAL DELAY plications can ensue, such as retinal detach- Evaluation of visual and auditory systems is ment or corneal exposure. Early intervention vital but, in our experience, is easily overlooked with copious ointment lubrication and, where by surgical teams intent only on achieving this is insufficient, lateral tarsorrhaphy, may survival from a major cardiac, choanal, or prevent corneal scarring and even perforation. tracheo-oesophageal repair. However, if all Assessment of visual function is important to handicaps can be defined early then steps can be maximise potential for education as spectacles made to locate the appropriate resources for or low visual aids may improve visual per- education as well as giving the parents as much formance. information as possible. The diagnosis of mental retardation should be made with caution in anyone with impaired hearing and vision as GENITOURINARY AND ENDOCRINE they are inherently understimulated. Deafness, ABNORMALITIES if not recognised early, may present with delay The presence of micropenis and undescended in language; poor vision may cause delay in fine testicles makes the early diagnosis of CHARGE motor skills. Children with both defective hear- Who's in CHARGE? Multidisciplinary management ofpatients with CHARGE association 223

ing and vision may present at an earlier date nose, and throat surgeon (as these patients are with delay in gross motor skills and problems also likely to have chronic ear problems includ- with balance. In some cases they may even ing hearing aid provision), the general paediatri- Arch Dis Child: first published as 10.1136/adc.65.2.217 on 1 February 1990. Downloaded from appear autistic. Mental retardation may be cian, and the district community paediatrician present but should only be diagnosed when the to be the most appropriate coordinators of- extent of the sensory deficit is known and when multidisciplinary long term management of the child has been in an adequate educational these patients. programme. We found, as with others,21 that major strides in development were often made 1 Hall BD. Choanal atresia and associated multiple anomalies. by patients with CHARGE association once Jf Pediair 1979;95:395-8. 2 Pagon RA, Graham JM, Zonana J, Young SL. Congenital parents realised that mental retardation was not heart disease and choanal atresia with multiple anomalies: inevitable and the potential of their children was CHARGE association. J Pediatr 1981;99:223-7. 3 Davenport SLH, Hefner MA, Mitchell JA. The spectrum of explained fully. We therefore consider that clinical features in CHARGE syndrome. Clin Genet mental retardation should not be used as one of 1986;29:298-310. 4 Oley CA, Baraitser M, Grant DB. A reappraisal of CHARGE the features of the CHARGE association. association. J7 Med Genet 1988;25:147-56. Instead, the term 'developmental delay' may be 5 Curatolo P, Libutti G, Brinchi V. Infantile spasms and the CHARGE association. Dev Med Child Neurol 1983;25: more appropriate. 367-73. Two patients attended special schools 6 Collum LMT. Uveal colobomata and other anomalies in three generations of one family. Br Jf Ophthalmol 1971;55: because of their small physique but relatively 458-61. mild sensory impairment. It is interesting that 7 Ho CK, Kaufman RL, Podos SM. Ocular colobomata, cardiac defect, and other anomalies: a study of seven cases when these children were first assessed develop- including two sibs. J7 Med Genet 1975;12:289-93. mentally (between 2 and 3 years old) they had 8 Hittner HM, Hirsch NJ, Kreh GM, Rudolph AJ. Coloboma- extremely poor scores, particularly in language tous microphthalmia, heart disease, hearing loss and mental retardation: a syndrome. J Pediatr Ophthalmol and fine motor coordination. Normal schooling Strabismus 1979;16:122-8. 9 Warburg M. Ocular coloboma and multiple congenital seemed out of the question and the parents were anomalies: the CHARGE association. Ophthal Paediatr advised of this. Subsequent assessments proved Genet 1983;2:189-99. 10 Mitchell JA, Giangiacomo J, Hefner MA, Thelin JW, this to be wrong. Slow initial development Pickens JM. Dominant CHARGE association. Ophthalmic may be a consequence of prolonged hospitalisa- Paediatr Genet 1985;6:31-6. 11 Metlay LA, Smythe PS, Miller ME. Familial CHARGE tion for major surgery in the first year of life syndrome: clinical report with autopsy findings. AMJt Med combined with lack of active management for Genet 1987;26:577-81. 12 De la Chapelle A, Herva R, Koivisto M, Aula P. A deletion in their sensory deficit. chromosome 22 can cause DiGeorge syndrome. Hum Genet 57:253-6. 13 Cyran SE, Martinez R, Daniels S, Dignan P St J, Kaplan S. Spectrum of congenital heart disease in CHARGE associa- WHO'S IN CHARGE? tion. J Pediatr 1987;110:576-8. 14 Lin AE, Chin AJ, Devine W, Park SC, Zackai E. The pattern Patients with CHARGE association require of cardiovascular malformation in CHARGE association. multidisciplinary management. This may be Am J Dis Child 1987;141:1010-3. 15 Siebert JR, Graham JM Jr, MacDonald C. Pathologic difficult to coordinate; surgical units receiving features of the CHARGE association: support for involve- sick neonates would do well to have a check list ment of the neural crest. Teratology 1985;31:331-6. 16 Brown OE, Burns DK, Smith TH, Rutledge JC. Bilateral of main and associated abnormalities to be posterior choanal atresia: a morphological and histologic http://adc.bmj.com/ investigated in dysmorphic children. Although study, and computed tomographic correlation. Intj Pediatr Otorhinolaryngol 1987;13:125-42. initial presentation of new patients is likely to be 17 Duncan NO, Miller RH, Catlin Fl. Choanal atresia and asso- for the management of congenital heart disease, ciated anomalies: the CHARGE association. Int3J Pediatr Otorhinolaryngol 1988;15:129-35. choanal atresia and/or tracheo-oesophageal 18 August PA, Rosebaum KN, Friendly D, et al. Hypopituitar- fistula, however, it seems inappropriate for ism and the CHARGE association. J Pediatr 1983;103: 424-5. cardiac or paediatric surgeons to coordinate 19 Pardo JM, Chua C. The CHARGE association in a male long term management of these patients. In our newborn infant. Clin Pediatr (Phila) 1989;24:531-3. 20 Burstein S, Grumbach MM, Kaplan SL. Early determination on September 24, 2021 by guest. Protected copyright. experience patients with choanal atresia gen- ofandrogen responsiveness is important in the management erally required more surgical procedures and of microphallus. Lancet 1979;ii:983-6. 21 Goldson E, Smith AC, Stewart JM. The CHARGE associa- investigations under anaesthetic. We would tion. How well can they do? Am J Dis Child 1986;140: therefore suggest the specialist paediatric ear, 918-21.