Indian Pediatrics 1999;36: 927-930

CHARGE Association

Ramesh Kumar, Bharat Balani, A.K. Patwari, S. Aneja and  V.K. Anand

From the Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi 110 001, India.
Reprint requests: Dr. A.K. Patwari, Flat No. 4, Lady Hardinge Medical College Campus, New Delhi 110 001, India.
Manuscript Received: January 18, 1999;
Initial review completed: February 18, 1999;
Revision Accepted: March 24, 1999

The charge association is an increasingly recognized non-random pattern of congenital anomalies comprising of Colobomata, Heart defect, choanal Atresia, Retarded growth and development, Genital hypoplasia and Ear abnormalities and/or deafness(1). These anomalies occur together more frequently than one would expect on the basis of  chance. In this communication we describe a boy with CHARGE association.

Case Report

A 9-year-old male child presented with complaints of recurrent abdominal pain. During examiantion the child was found to have abnormal facies. It inspired us for a detailed history and examination. The child was a product of full term vaginal delivery with uneventful antenatal and perinatal history. There was no history of drug intake or radiation exposure in antenatal period. Family history was not significant. History of deviation of left eye was found in infancy, for which surgery was done. Records of this surgery were not available. According to mother, there was global delay in achieving milestones and a child was not growing properly in comparison to peers of his age. There was no history of feeding problems during infancy.

Physical examination of the child at the time of presentation revealed a short statured child with obvious facial dysmorphism. Anthropometry showed weight of 16 kg (<5th percentile), height 109.5 cm (<5th percentile) and head circumference 50.5 cm. The child had a wide nasal bridge with pinched nose, microphthalmia, obvious squint in left eye, microcornea and bilateral iris coloboma (Fig. 1).

Photograph showing facial features with coloboma of iris and squint in left eye of the patient.

Fig. 1. Photograph showing facial features with coloboma of iris and squint in left eye of the patient.

The examination of ears revealed abnormality in the form of lobeless pinna and trian gular concha which was present bilaterally. The child also had bilateral cryptorchidism, hypoplastic nails and irregular dentition. The systemic examination was within normal limits. There was no evidence of choanal atresia on examination. Laboratory investigations including hematological and biochemical parameters were within normal limits. Skeletal survey showed no abnormality. Fundus examination was within normal limits. IQ testing showed a normal intelligence but there was poor school performance. Ultrasound abdomen revealed absence of right kidney which was confirmed by intra-venous pyelography. Echocardiography and audiometry revealed no abnormality. Thyroid function tests were within normal limits. The chromosomal analysis revealed 44 XY chromosome constitution performed using GTG banding technique. An upper gastrointestinal endoscopy for recurrent abdominal pain revealed antral gastritis with H. pylori infection on histopathological studies. Patient was advised multivitamins and a regular followup.

This child had a combination of congenital anomalies, characteristic facies, bilateral iris coloboma, ear anomalies, retardation of growth and development, genital hypoplasia, renal agenesis, which is consistent with diagnosis of CHARGE association.


CHARGE association was first described by Hall in 1979 in children with multiple congenital anomalies who were ascertained because of choanal atresia(2). But it was Pagon et al. in 1981 who first coined the acronym CHARGE association(1). This multiple congenital anomaly condition has an estimated prevalence of 1:10,000(3). To improve the diagnostic accuracy, various diagnostic criteria have been proposed for CHARGE assocation. Pagon et al proposed that to make a confident diagnosis of the CHARGE association at least four of the seven major features included in the memonic have to be present and these should include either coloboma or choanal atresia or both(1). Mitchell et al. in 1985 proposed a revised diagnostic criteria to allow one to make a definite, probable and possible diagnosis of CHARGE association(4).

Recently revised consensus diagnostic criteria have been proposed which incorporate both major and minor features for CHARGE association both to enhance clinical diagnosis and facilitate research efforts(3). According to these criteria, the diagnosis of CHARGE association should be considered in any in-fant with one or two major and several minor characteristics(3). Our patient had two major characteristics_bilateral iris coloboma and external ear anomalies and three minor characteristics. He had distinctive face, bi- lateral cryptorchidism suggestive of genital hypoplasia, developmental delay and growth retardation. In addition, our patient also had right renal agenesis and nail hypoplasia which has also been reported by earlier workers in CHARGE association(5).

Eye malformations have been reported in as high as 80% of patients with CHARGE association. Besides coloboma, which is most common, microphthalmia, anisometropia and strabismus are also known to occur. Coloboma may be unilateral or bilateral and may effect only iris or extend to involve retina in which case vision in usually impaired(6). Our patient had microphthalmia, microcornea with bilateral iris coloboma and strabismus in left eye.

Distinctive ear anomalies are found in 90% patient with CHARGE assocication. The most common abnormality is small, square or triangular and apparently low set ears with simple helices and small or absent lobes. CHARGE child may also have structural deformity of middle/inner ear leading to conductive or sensorineural deafness(7,8). Our patient had lobeless ears and triangular choncha but there was no deafness. Choanal atresia either unilateral or bilateral is seen in 50-60% of CHARGE patients. Though bi- lateral choanal atresia is usually diagnosed in neonatal period, unilateral atresia may remain undiagnosed unless specifically looked for(3). Choanal atresia was not found in our patient.

Congenital heart defects occur in 50-80% of patients with CHARGE. Defects include tetralogy of Fallot (commonest), AV canal malformation and L-R shunts(9). Echocardio-graphy was normal in our patient. Growth retardation is a frequent problem in children with CHARGE association. These children are usually normal at birth but later on show growth retardation owing to repeated infections, feeding problems and frequent surgeries(10). Cranial nerve palsies (involving VII, VIII and IX cranial nerves), renal anomalies (agenesis, malrotation, horse-shoe kidney, hydronephrosis) and genital hypoplasia (micropenis, cryptorchidism, labial hypo-plasia) are other frequent associations seen in a child with CHARGE association(3). Our patient had unilateral renal agenesis with bilateral cryptorchidism. Table I summarizes the frequency of anomalies associated with CHARGE association as reported by various authors.

The etiology of the CHARGE association remains unknown. Most cases are sporadic, although there are rare familial cases suggestive of autosomal recessive or dominant transmission. Unbalanced translocation at t (2;18), t(3:22), t(6:8) and microdeletion in 22q 11.2 region resulting in infants with phenotypic findings of CHARGE association have been reported indicating genetically heterogenous condition(12). Phenotypically, CHARGE association resembles other malformation syndromes like DiGeorge syndrome, VACTERL association, Velocardio-facial syndrome (VCFS) and retinoic acid embryo-pathy. These should be considered in differential diagnosis of a CHARGE association.

Table I__Frequency (%) of Various Anomalies in CHARGE Association.

Author Coloboma Choana





   Pagon et al.(1)







Harvey et al.(5)







Christine et al.(11)







The key to management of a child with CHARGE association is early identification, evaluation of the specific defects and needs, and comprehensive intervention and ongoing monitoring. Early management of heart and visual defects, coexisting medical/surgical problems and adequate feeding and nutrition helps making the life simple for these children. A multidisciplinary approach involving specialists from different fields with a pediatrician leading and coordinating them is often helpful in proper management of these children.


1. Pagon RA, Graham JM, Zoana J, Yong SL. Coloboma, Congenital heart disease and choanal atresia with multiple abnormalities - CHARGE association. J Pediatr 1981; 99: 223-227.

2. Hall BD. Choanal atresia and associated multiple anomalies. J Pediatr 1979; 95: 395-398.

3. Blake KDI. Davenport SL, Hall BD, Hefner MA, Pagon RA, Williams MS, et al. CHARGE association: An update and review for the primary pediatrician. Clin Pediatr 1998; 37: 159-171.

4. Mitchell JA, Davenport SL, Hefner MA, Shei MM.Use of an expert system to test diagnostic criteria in CHARGE syndrome. J Med Systems 1985; 9: 425-436.

5. Oley CA, Baraitser M, Grant DB. A reappraisal of CHARGE association. In: Congenital Malformation Syndromes. Eds. Donnal D, Winter RM. London, Chapman and Hall Medical, 1995; pp 455-473.

6. Russell-Eggin IM, Blake KDI Taylor DSI Wyse RKH. The eye in the CHARGE association. Br J Ophthalmol 1990; 74: 421-426.

7. Davenport SLH, Hefner MA, Thelin JW. CHARGE Syndrome. Part I. External ear anomalies. Int J Pediatr Otorhinolaryngol 1986; 12: 136-143.

8. Thelin JW, Mitchell JA, Hefner MA. CHARGE Syndrome. Part II. Hearing loss. Int J Pediatr Otorhinolaryngol 1986; 12: 145-163.

9. Wyse RKH, Al-Mahdawi S, Burn J, Blake KO. Congenital heart disease in CHARGE association. Pediatr Cardiol 1993; 14: 75-81.

10. Blake KD, Kirk JMQ, Ur E. Growth in CHARGE association. Arch Dis Child 1993; 68: 508-509.

11. Harvey AS, Leaper PM, Bankier A. CHARGE association: Clinical manifestations and developmental outcome. Am J Med Genetics 1991; 39: 48-55.

12. North KN, Wu BL, Cao BN, Whiteman DA, Korf BR. Charge association in a child with de novo inverted duplication (14) (q2-q24.3). Am J Med Genetics 1995; 57: 610-614.

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