Indian Journal for the Practising Doctor

Vaghela J, Sharma R

Dr. Jignesh Vaghela, D Ped, Consultant Pediatrician, Bhuta Hospital, Bhavnagar (Gujarat);
Dr. Rashmi Sharma, MD, (PSM), Associate Professor, Community Medicine Department, Kesar SAL Medical College, Ahmedabad (Gujarat).

Correspondence: Dr Rashmi Sharma, 12, Shrestha Bungalows, Near Shrushti Arcade, Motera Gandhinagar Highway, Ahmedabad-382424, [Fax No. 079 2; e mail: drrashmi_psm(at)yahoo.com]

ISSN: 0973-516X

Abstract

We report a case of ‘CHARGE Syndrome’ seen in a neonate delivered at the Bhuta Hospital in the remote town of Sihor (District Bhavnagar) from a G2 P2 A0 mother. The child presented with coloboma of iris, bilateral choanal atresis, retrognanthia, low posterior hair line, short nose, bulging mobile chest, flat abdomen, poorly developed scrotum with undescended testis, and micropenis. The child died on the second day of life.

Key words: Newborn, Charge syndrome

‘CHARGE Syndrome’ was initially defined as a non-random association of anomalies (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness). ‘CHARGE’ is an acronym for coloboma, heart defect, atresia choanae, retarded growth and development, genital abnormality and ear abnormality. In 1998, an expert group defined the major criteria (classical 4C’s: choanal atresia, coloboma, characteristic ears and cranial nerve anomalies) and minor criteria of the CHARGE syndrome. Individuals with all the four major characteristics or three major and three minor characteristics are highly likely to have CHARGE syndrome; the diagnosis is based on a combination of major and minor characteristics.

Case Report

A male baby was delivered by a 23 year old nonworking mother, literate up to X standard and married to a 28 year old labourer with active married life for the last six years. There was no history of consanguineous marriage. The antenatal period was uneventful. The woman received 3 antenatal visits with 2 doses of tetanus toxiod and iron folic acid (IFA) supplements. Ultrasonography (USG) was not done during pregnancy as the couple refused for it. No history of tuberculosis, diabetes, hypertension, smoking, alcohol intake or taking any teratogenic drugs during pregnancy was given. There was no genetic disorder in family, and also no febrile illness during pregnancy was reported. There was no history of any family planning device usage. It was a pre term (34-36 wks) delivery and the birth weight was 2.1 kilograms.

On examination, the baby was pale and did not cry after birth and there was no spontaneous respiration. There was bradycardia and cyanosis. The baby had many malformations which included coloboma of iris, bilateral choanal atresis, short hands, retrognanthia, low posterior hair line, short and broad nose, bulging mobile chest, flat abdomen, poorly developed scrotum with un-descended testis, micropenis and sandle gap between great and second toe (Figure 1 and 2).

As part of the management, for bradycardia and cyanosis the baby was intubated – bag and tube ventilation was given for 2 minutes and spontaneous respiration came but with distress. Cyanosis was still there so baby was shifted to nursery under warmer care. The cyanosis gradually disappeared but the distress was still there. Intravenous fluids (10% dextrose) with calcium were started and vitamin K was given. The baby was then investigated. Chest radiograph was apparently normal. On ultrasonography both the testis were not visualized in the scrotal sac or the inguinal canal; rest of the organs were normal. Echocardiography and genetic study was not done because of the refusal by parents. Next day the parents asked for discharge against medical advice. The baby died on the second day of life.

Discussion

The reported incidence of CHARGE Syndrome ranges from 0.1 to 1.2/10,000 and depends primarily on professional recognition. It is not known to be related to any illness, exposure to drugs or alcohol intake during pregnancy, and typically it does not occur to more than one person in a family. It is very rare, and cannot be predicted. Coloboma mainly affects the retina. Major and minor congenital heart defects (commonest cyanotic heart defect is tetralogy of Fallot) occur in 75–80% of patients. Choanal atresia may be membranous or bony, bilateral or unilateral, and is present in 50 – 60 percent of cases. Mental retardation (ranging from minimal to profound retardation) is another common feature. Under-development of external genitalia is a common finding in males but is less apparent in females. Ear abnormalities include classical finding of unusually shaped ears and hearing loss (conductive and/or nerve deafness resulting mild to severe deafness).

The cause of CHARGE is not known. Mutations in CHD7 gene cause more than half of all cases. This gene provides instructions for making a protein that regulates gene activity by a special process (chromatin remodeling). Mutations in CHD7 gene lead to the production of an abnormally short, nonfunctional CHD7 protein, which disrupts chromatin remodeling and the regulation of gene expression. However, about one-third of individuals with CHARGE syndrome do not have an identified mutation in the CHD7 gene. The affliction is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the CHD7 gene and occur in people with no history of the disorder in their family.

The condition needs to be differentiated from the 22q deletion syndrome which has many of the same features but the face, hands and ears look different. Special FISH test can diagnose 22q deletion. Patients with Kabuki syndrome also have many of similar medical and behavioral features, however, eyes and fingertips are different and puberty is early in Kabuki syndrome. The ears, face and hand do not look like those in the CHARGE syndrome.

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