Neonatal imaging: Diagnosis
1 Lake Smit and Partners, Durban, South Africa
2
Parklands
Hospital, Durban, South Africa
We
congratulate Dr Saifullah Khalid, Department of
Radiodiagnosis, Jawaharlal Nehru Medical College, Aligarh
Muslim University, Aligarh, Uttar Pradesh, India, for her
excellent diagnosis, for which she receives the award of R1
000 from the RSSA. Notable second-place entries were made by
Drs Aadil Ahmed, Samuel Manikkam, Jacqueline du Toit,
Phil Harries-Jones and Shaun Scheepers. Drs Misser
et al. elaborate below on the images
and findings. Please refer to page 116 of the August 2013
issue of the SAJR (http://dx.doi.org/10.7196/SAJR.934)
for the presenting details and the investigative images.
S Afr J Rad 2013;17(4):154-156.
DOI:10.7196/SAJR.1020
Diagnosis
Imaging and findings
This first set of radiographs was taken of a neonate born at 33 weeks’ gestation. Birth weight was 1.5 kg and the initial Apgar scores were satisfactory. Respiratory distress and bile-stained nasogastric returns were noted post-delivery. Fig. 1 is a plain abdominal radiograph showing the umbilical venous line, right femoral peripheral line to the IVC and a nasogastric tube with tip in the distended pyloric antrum. ‘Double bubble’ configuration of the stomach and first segment of the duodenum is noted. The rest of the abdomen is gasless. Incidental note is made of the hemivertebra of the tenth dorsal level with missing ipsilateral left tenth rib. Slight angulation of the sacral tip to the right is also identified. The lateral shoot-through (Fig. 2) confirms the bowel abnormality and the apparent anomaly of the forearm bones with club hand configuration. This is confirmed on the babygram image (Fig. 3) where the left radius and thumb is noted to be absent (type IV radial club hand deformity). In addition, the moderate cardiomegaly and plethoric appearance of the lung fields raise suspicion for an intracardiac left-to-right shunt (e.g. atrioventricular septal defect/AVSD) or patent ductus arteriosus (PDA). The gastroduodenal distension, D10 hemivertebra, gentle rightward scoliosis, absent left tenth rib and sacral angulation are all again noted. Fig. 4 reveals a harlequin deformity of the orbits, which is associated with craniosynostosis of the coronal suture or plagiocephaly.
Clinical examination of the child noted the
abnormality of the left forearm and wrist with club hand
deformity, a sacral pit and a systolic cardiac murmur. There was
no marked brachicephaly or other cranial deformity. The
respiratory distress was managed as for surfactant deficiency
disease, a surgical opinion was sought regarding the bowel
abnormality, and a full cardiac assessment was arranged. The
echocardiogram revealed three left-to-right shunts including an
ASD, ventricular sepal defects (VSD) and a large PDA. The
duodenal atresia was successfully corrected and the
post-operative period was uneventful. Further investigation
included chromosomal studies, which were negative for major
chromosomal abnormalities. The combination of all the
clinico-radiographic findings made VACTERL association (VA)
(Vertebral anomalies, Anal atresia, Cardiac defects,
Tracheoesophageal fistula and/or Esophageal atresia, Renal
anomalies and Limb defects) the most likely diagnosis. Fanconi
anaemia is an important diagnosis to exclude by relevant
testing. The apparent harlequin deformity was probably
incidental, but may be a feature of Baller-Gerold syndrome,
which has a few overlapping features with VA. In the last month,
the baby had successful cardiothoracic surgery for correction of
the septal defects and is currently recovering well. Further
management includes future orthopaedic mangement of the left
upper limb deformity.
Discussion
VA is the expanded acronym for the
nonrandom association of multiple birth defects originally
described as the VATER syndrome.1 The
term ‘association’ is thought to be more appropriate than a
syndrome as the features are not pathogenetically linked but
rather tend to occur more frequently in such a group than in the
general population. The abnormalities are predominantly of
structures derived from the embryonic mesoderm. Table 1 outlines
the various systemic abnormalities that are associated with the
VACTERL constellation. A diagnosis of VA is made if at least
three of the clinical associations are present.
Genetics
Most cases of VA are sporadic. The condition rarely occurs twice in a family. The incidence is estimated at 1.6 in 10 000 live births. No specific gene locus has been identified, but there are several genes implicated in this condition. Sonic hedgehog gene (SHH), for instance, is regarded as a keystone sequence, especially in those patients with oesophageal atresia and anorectal malformations.2 SHH encodes for an intracellular signaling protein vital for embryogenesis. Early disruption of the mesodermal differentiation in utero at the first 5 weeks has been suggested as the basis for the nonrandom association of VA.3
In
addition, VA is known to occur more frequently in infants born
to diabetic mothers.4 Microdeletions of the FOX gene cluster at chromosome 16,
long arm deletions of chromosome 13 and 12 as well as trisomy
of chomosome 18 have been implicated among other gene defects.
Vertebral defects
These are probably the most common association
in VA. The spectrum includes segmentation anomalies such as
hemivertebrae, fused vertebrae or hypersegmentation. Any
combination of vertebral and other skeletal anomalies is seen,
especially rib and sternal abnormality. Cord tethering and
sacral abnormalities also occur more frequently. The vertebral
defects rarely account for mortality in these patients.
Recently, sonar has been introduced as a useful modality in the
assessment of vertebral defects.
Anorectal malformations
The presence of an anorectal abnormality is
clinically apparent in the first few days of life and usually
requires early surgical correction. Some children will require
repeat corrective or reconstructive surgical procedures.
Cardiac defects and vascular anomalies
In many
series of VA, congenital cardiac abnormalities prove to be the
most common associated defect. Intracardiac shunts,
particularly VSD, are seen frequently. In most patients, the
VSD is generally one of several cardiac defects present,
rarely found in isolation. The single umbilical artery was
noted to be present more commonly in VA, and it was suggested
by Temtamy et al.4 shortly after the initial
description that V in VATER should include vascular, in
addition to vertebral abnormalities.
Tracheo-oesophageal fistula and atresia
These foregut abnormalities occur variably in
50 - 80% of patients with VA.5 Antenatal sonar diagnosis of
polyhydramnios or absence of the stomach fluid echo should alert
the obstetrician to look for other possible congenital
abnormalities. Early post-partum surgery is indicated after the
subtype of foregut anomaly is determined. Early and late
neonatal complications including chest infections are an
important cause of co-morbidity.
Renal abnormalities
These may be less apparent than other
components of VA, and dedicated imaging of the renal tract may
be required to elucidate such anomalies. Structural renal
malformations may be a significant cause of morbidity,
particularly recurrent infections and premature renal failure.
Limb defects
Several limb malformations have been added to
the list of possible appendage defects. The classic description
included radial ray anomalies also known as radial club hand.
Classifications of this deformity originally described with
gradation of mild to severe radial aplasia have been revised
with several additions, including recent inclusion of a fifth
sub-type of absent radius with associated deficiency of the
humerus and variable involvement of carpal bones.
Differential diagnosis
There is considerable overlap between the
various syndromes; subtle findings on clinical examination,
imaging and laboratory testing will enable a final diagnosis.
Proper diagnosis aids further adequate genetic counseling of
families. Table 2 delineates the main distinguishing features in
the major differential diagnoses, which include Fanconi anaemia,
Feingold syndrome, Charge syndrome, DiGeorge syndrome (or
22q11.2 deletion syndrome), oculo-auriculo-vertebral syndrome,
Currarino syndrome and VACTERL H. In South Africa, the relative
increased incidence of Fanconi anaemia in our population of
Afrikaner descent must alert the clinician to the relevant
testing in any patient with features of VA owing to the
considerable overlap of features, especially the radial ray
abnormality. The recessive inheritance pattern, propensity for
malignancies in early adulthood and shortened lifespan of
patients with Fanconi anaemia warrants early diagnosis of this
entity, as genetic counselling is increasingly being offered to
affected families.
Management and prognosis
The management of patients with VA depends on
the attendant components of the spectrum present at birth. Major
life-threatening malformations require urgent neonatal surgical
attention. Orthopaedic treatment of limb abnormalities and
corrective surgeries for cardiac malformations and scoliosis may
be planned/staged in several surgical procedures. The vast
development in specialised neonatal and post-surgical ICU
facilities has resulted in a better overall prognosis in the
managed VA child. The subsequent long-term prognosis is variable
and highly dependent on the severity of the individual
components in the patient. In addition, each patient will have
to endure a further list of complications, related to the
component encountered, throughout life. Particular note must be
made of the normal neurocognitive functioning in patients with
VA. This is a significant positive feature. Some patients may
have a normal lifespan without life-threatening issues, but the
vast majority will require close surveillance for complications
owing to significant associated morbidity.
1. Quan L, Smith DW. The VATER association: Vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, radial dysplasia. In: The Clinical Delineation of Birth Defects. Volume XII. G.I. Tract Including Liver and Pancreas. Bergsma D, ed. Baltimore: Williams and Wilkins, 1972:75-78.
2. Martinez-Frias M L, Bermejo E, Frias JL. The VACTERL association: Lessons from the sonic hedgehog pathway. Clin Genet 2001;60:397-398.
3. Khoury MJ, Cordero JF, Greenberg F, James LM, Erickson JD. A population study of the VACTERL association: Evidence for its etiologic heterogeneity. Pediatrics 1983;71:815-820.
4. Temtamy SA, Miller JD. Extending the scope of the VATER association: Definition of the VATER syndrome. J Pediatr 1974;85:345-349.
5. Solomon BD. VACTERL/VATER association. Orphanet Journal of Rare Diseases 2011;6:56