SAJR 1020

Neonatal imaging: Diagnosis

S K Misser,1 MB ChB, FC Rad (D) SA; T A Mitha,2 BSc, MB ChB, FCP (SA) Paed; A S Shaik,2 MB ChB, FCS (SA), Cert (Paed Surg) SA

1 Lake Smit and Partners, Durban, South Africa

2 Parklands Hospital, Durban, South Africa

Corresponding author: S K Misser (misser@lakesmit.co.za)


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.

    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.

    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.

    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.

    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

    5. Solomon BD. VACTERL/VATER association. Orphanet Journal of Rare Diseases 2011;6:56



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