CHARGE Syndrome
Author(s): Vaghela J, Sharma R
Vol. 5, No. 6 (2009-01 - 2009-02)
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.
References:
- Pagon RA, Graham JM Jr, Zonana J, Yong
SL. Coloboma, congenital heart disease, and
choanal atresia with multiple anomalies:
CHARGE association. J Pediatr. Aug 1981;99
(2):223-7.
- Blake KD, Davenport SL, Hall BD, Hefner
MA, Pagon RA, Williams MS. CHARGE
association: an update and review for the
primary pediatrician. Clin Pediatr
(Phila). Mar 1998; 37 (3):159-73.
- Issekutz KA, Graham JM Jr, Prasad C, Smith
IM, Blake KD. An epidemiological analysis of
CHARGE syndrome: preliminary results from a
Canadian study. Am J Med Genet A. Mar
15 2005; 133A (3):309-17.
- Vissers LE, van Ravenswaaij CM, Admiraal R,
et al. Mutations in a new member of the
chromodomain gene family cause CHARGE
syndrome. Nat Genet. Sep 2004;36(9):955-7
- Aramaki M, Udaka T, Kosaki R, Makita Y,
Okamoto N, Yoshihashi H. Phenotypic
spectrum of CHARGE syndrome with CHD7
mutations. J Pediatr. Mar 2006; 148 (3):410-4.
- Jongmans MC, Admiraal RJ, van der Donk KP,
et al. CHARGE syndrome: the phenotypic
spectrum of mutations in the CHD7 gene. J
Med Genet. Apr 2006;43(4):306-14.
- Lalani SR, Safiullah AM, Fernbach SD, et
al. Spectrum of CHD7 Mutations in 110
Individuals with CHARGE Syndrome and
Genotype-Phenotype Correlation. Am J Hum
Genet. Feb 2006; 78 (2):303-14.
- Tellier AL, Cormier-Daire V, Abadie V, et
al. CHARGE syndrome: report of 47 cases and
review. Am J Med Genet. Apr
13 1998;76(5):402-9.
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.
References:
- Pagon RA, Graham JM Jr, Zonana J, Yong SL. Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. J Pediatr. Aug 1981;99 (2):223-7.
- Blake KD, Davenport SL, Hall BD, Hefner MA, Pagon RA, Williams MS. CHARGE association: an update and review for the primary pediatrician. Clin Pediatr (Phila). Mar 1998; 37 (3):159-73.
- Issekutz KA, Graham JM Jr, Prasad C, Smith IM, Blake KD. An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study. Am J Med Genet A. Mar 15 2005; 133A (3):309-17.
- Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. Sep 2004;36(9):955-7
- Aramaki M, Udaka T, Kosaki R, Makita Y, Okamoto N, Yoshihashi H. Phenotypic spectrum of CHARGE syndrome with CHD7 mutations. J Pediatr. Mar 2006; 148 (3):410-4.
- Jongmans MC, Admiraal RJ, van der Donk KP, et al. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. Apr 2006;43(4):306-14.
- Lalani SR, Safiullah AM, Fernbach SD, et al. Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation. Am J Hum Genet. Feb 2006; 78 (2):303-14.
- Tellier AL, Cormier-Daire V, Abadie V, et al. CHARGE syndrome: report of 47 cases and review. Am J Med Genet. Apr 13 1998;76(5):402-9.