Correspondence and Reprint requests : Dr. Pankaj B Agrawal,
Children’s Hospital Boston, 300 Longwood Avenue, Hunnewell 4,
Boston, MA, USA.
[DOI-10.1007/s12098-009-0232-9]
[Received November 12, 2008; Accepted December 29, 2008]
Clinical Brief
Novel
CHD7
and
FBN1
Mutations in an Infant with
Multiple Congenital Anamolies
Chia-Hua Chiu
1
, Joseph Thakuria
2
and Pankaj B. Agrawal
1,2
1
Divisions of Newborn Medicine and
2
Genetics, Department of Medicine, Children’s, Hospital, Boston, MA, USA
ABSTRACT
The first case of an infant with a dual genetic diagnosis of CHARGE and Marfan syndrome is reported here. The patient had
multiple congenital anamolies, many of them consistent with CHARGE syndrome and genetic testing identified a
heterozygous mutation c.3806_11del6insA in the CHD7 gene. In addition, his father had physical features consistent with
Marfan syndrome. Fibrillin-1 (FBN1) mutation screening identified a heterozygous c.3990insC mutation in both father and
the patient. [Indian J Pediatr 2010; 77 (2) : 208-209]
Email: pankaj.agrawal@childrens.harvard.edu
Key words: CHARGE syndrome; CHD7; FBN1; Marfan syndrome
CHARGE syndrome (MIM 214800) is characterized by a
constellation of clinical findings that include coloboma,
choanal atresia, cranial nerve dysfunction, ear
abnormalities, genital hypoplasia, cardiovascular
malformations, growth deficiency and
tracheoesophageal fistula.
1
The syndrome was first
reported in 1979. Since then, clinical findings
associated with this syndrome have been extensively
described and in 2004, heterozygous mutations in the
CHD7 gene were identified
CHD7 mutations are
responsible for about 60% of the cases with CHARGE
syndrome. FBN1 is the only gene known to be
associated with Marfan syndrome (MS) and mutations
of this gene are responsible for 70-93% of the cases.
3
Here is reported the first case of an infant with multiple
congenital anamolies carrying heterozygous mutations
of both the CHD7 and FBN1 genes.
REPORT OF CASE
The male patient was born at 37 wk gestation. The
pregnancy was complicated by polyhydramnios and
fetal growth restriction. At birth, he was noted to have
multiple congenital anomalies that included crumpled
ears, left facial palsy, micropenis, and long fingers and
toes (Fig. 1a-c). Birth weight was 2.035 kg, height 43 cm
and head circumference 31 cm. Excessive oral
secretions and inability to pass a nasogastric tube in
stomach raised suspicion for esophageal atresia (EA).
Radiographic findings were consistent with EA and
tracheoesophageal fistula (TEF). His echocardiogram
revealed bicuspid aortic valves, atrial septal defect,
patent ductus arteriosus, and a left-sided aortic arch
with an aberrant right subclavian artery. He underwent
repair of EA/TEF on day of life (DoL) 2.
Fig. 1. Phenotypic features and upper gastrointestinal (UGI)
radiographic study of the patient. His facial features
included crumpled ears (Panel A). He had long, slender
fingers (Panel B). Genital hypoplasia was also present
(Panel C) with stretched penile length of 2 cm. Panel D
demonstrates intrathoracic stomach (arrow) on UGI study.
208 Indian Journal of Pediatrics, Volume 77—February, 2010