Oesophageal atresia (EA) and tracheoesophageal fistula (TEF) is one of the congenital anomaly occurring in the newborns with the incidence of 1 in 2500 births seen worldwide. A retrospective review of newborns admitted to Hospital Sultanah Bahiyah (HSB) from 1st January 2000 to 31st December 2009 was done. The objective was to look at the influence of birth weight, time of surgical intervention, presence of other congenital anomaly and presence of preoperative pneumonia to the immediate outcome (mortality) of the surgery. There were 47 patients with oesophageal atresia, out of which 26 (55%) were males and 21 (45%) females. The distribution of patients by race were 34 Malays (72%), 9 Chinese (19%) and 4 Indians (9%). The birth weight of the babies range from 0.8 kg to 4.0 kg and there was a significant association with the outcome of the surgery (p< 0.05). Most of the babies (20) were operated within 24 hours of presentation but there was no significant association to the outcome. 23 (49%) of them were born with congenital malformation and there was a significant association with the outcome of the surgery (p<0.05). Based on the chest roentgenogram, 20 (43%) of them had pneumonia with significant association with the outcome (p<0.05). The mortality rate is 23% and the causes of death were pneumonia (36%), renal failure (18%), cardiac malformation (18%) and multiple congenital malformations (28%). The outcome of EA and TEF is determined mainly by birth weight, congenital malformations and presence of preoperative pneumonia in HSB.
VACTERL association is a rare genetic disorder involving at least three of the following congenital
malformations: vertebral defects (V), anal atresia (A), cardiac defects (C), trachea-oesophageal fistula with
or without oesophageal atresia (TE), renal anomalies (R) and limb abnormalities (L). Until now, the
aetiology of VACTERL association is unknown, particularly at the molecular level. Here, we performed
whole exome sequencing (WES) of an infant with VACTERL association. The patient was delivered
prematurely at 30 weeks and had 4/6 of the VACTERL malformations. Trio-WES analysis was performed
using Torrent Suite and ANNOVAR. Polymorphisms with an allele frequency of >0.01 were excluded, and
the remaining variants were filtered based on de novo mutations, autosomal recessive, X-linked and di-genic
inheritance traits. In this patient, no homozygous, compound heterozygous or X-linked mutations was
associated with VACTERL. However, we identified two heterozygous mutations; KIF27
(ENST00000297814: c.3004A> C:p.N1002H) and GNAS (ENST00000371098: c.205C>A:p.H69N) genes that
were inherited from her father and mother respectively. A de novo, IFT140 gene mutation
(ENST00000426508: c.683C>G:p.S228C) was also identified in this patient. The VACTERL phenotype in
this patient may due to heterozygous mutations affecting KIF27 and GNAS genes, inherited via autosomal
recessive trait. In addition, the IFT140 gene mutation may also be involved. These genes are known to be
directly or non-directly involved in the sonic hedgehog signalling that is known to be implicated in
VACTERL. This is the first report of these genetic mutations in association with VACTERL.