VACTERL is a well-known acronym for V (vertebral anomalies), A (anal malforma-tions), C (cardiac anomalies), TE (tracheo-esophageal fistula or esophageal atresia), R (renal/urinary anomalies) and L (limb defect)(1). It is a classical example of a non-random association of malformations. Numerous minor anomalies and their interrelationship with other phenotypes have been documented in leterature(2). We report a typical case of VACTERL phenotype to highlight three interesting and unusual findings occurring in the same patient viz., hemifacial microcosmia (HFM), pseudo-extrophy of the urinary bladder and an urachal cyst communicating with the bladder.

A baby girl M was born at term gestation to a 28-year-old primigravida mother with an uncomplicated antenatal period. She was a small for gestational age baby weighing 2350 grams at birth. There was no history of exposure to any known teratogen. The ante-natal ultrasound examinations (done at 20 and 34 weeks) were reportedly normal. The baby did not suffer perinatal asphyxia. A single umbilical artery was noted at the time of birth.

On examination, her length was 42 cm (<10 centile), occipitofrontal circumference was 32 cm (10 centile) and ponderal index was 3.1. The face was asymmetric with reduced bony prominences, deformed hypoplastic pinna and microtia on the left side. The infant also had a short neck and a cord like hypoplastic left sternocleidomastoid muscle causing torticollis. She had an anal stenosis with an anteriorly placed anoperineal fistula, an inferiorly placed umbilicus, an umbilical swelling, a thin infra-umbilical anterior abdominal wall and a skin defect extending from umbilicus to pubis (Fig. 1).

Fig. 1. Anal stenosis, anteriorly placed anoperineal fistula and umbilical swelling.

Skiagrams of lumbar and thoracic vertebrae showed multiple vertebral body clefts. An abdominal ultrasonogram showed an intact but hypoplastic anterior abdominal wall and wide pubic bone separation. This was consistent with pseudoextrophy of urinary bladder. The umbilical swelling contained a urachal cyst, which commu-nicated with the bladder. The kidneys, female genital organs and other abdominal structures were normal. The echocardiogram identified an ostium secondum atrial septal defect. The cranial ultrasonography, indirect laryngo-scopy, opthalmological examination and karyotyping were all normal.

On the basis of phenotypic features a diagnosis of VACTERL-HFM phenotype was made. She started accepting breast feeds from day one and passed urine normaly. An anal dilatation program with Hegar dilators was started along with urinary antibiotic prophylaxis. During the follow up, we plan to do a bronchoscopy to rule out H type trachea-esophageal fistula and contrast studies to rule out vesico-ureteric reflux and structural anomalies in the urinary tract. She is also under surgical follow up. Excision of the urachal cyst, surgery for anal stenosis and facial reconstructive surgery is planned at the appropriate ages.

Our patient had the following features that clinched the diagnosis of VACTERL; vertebral body defects, anal malformation, cardiac defects, renal/urinary malformation and single umbilical artery. Numerous associated anomalies that occur less frequently have also been described(1,2). The interrelationship of VACTERL phenotype with HFM has been observed in the past(3). The HFM phenotype by itself represents a spectrum of congenital malformations involv-ing embryological derivatives of the first and second branchial arches(4). Patients usually have unilateral microtia, macrostomia and failure of formation of the mandibular ramus and condyle. Our index patient was diagnosed to have HFM on the basis of unilateral hypoplasia of the facial bones, ear and sternocleidomastoid muscle. Although HFM is included under the umbrella of oculo-auriculo vertebral spectrum(5) and can occasionally have all the malformations as described in our case, anorectal malformation has not been described, which substantiates the diagnosis of VACTERL HFM pheno-type.

Associations are derivatives of casually nonspectific disruptive events (defective mesodermal development, failure of apoptosis or initiation of malformation sequences) acting on the developmental field (during first 4 weeks of life the entire embryo constitutes a development field)(6). The above concepts have been derived from epidemiological observations(2,6) or by extrapolation of studies conducted on animals e.g., adriamycin induced VACTERL association in rats(7), and at present is largely hypothetical. Probably a severe exposure in the early phases of blastogenesis to either a determined or undetermined causative factor induces severe form of disruptive event e.g., VACTERL + charge + murc association in the same case or VACTERL in association with other phenotypes like HFM, sacrococcygeal dysgenesis(8) or sirenomelia(9), where as a milder exposure acting in later phases of blastogenesis would result in pure VACTERL or subset of VACTERL association. The nature of malformations in both the phenotypes (VACTERL and HFM) can be attributed to their relative location in the sequence of normal cranio-caudal human embryologic development(3). Thirteen percent of 247 patients with HFM were found to have VACTERL association in one of the study while analyzing the interrelationship between VACTERL and HFM phenotype(3). Abnormalities related to the blood vessels and heart were commoner in VACTERL-HFM phenotype than in the individual phenotypes. This is attributed to the involvement of neural crest in the pathogenesis of both HFM and conotruncal defects(3).

The other interesting finding was the presence of pseudoexstrophy (covered exostrophy)(10) of the urinary bladder along with an umbilical swelling containing an urachal cyst and communicating with the bladder. These features (pseudoexstrophy bladder+urachal cyst + VACTERL – HFM) are exceedingly rare and have not been reported together in any single case so far(10).

The outcome in these cases depends on the severity of individual problems and the presence of underlying chromosomal abnor-malities. Heart failure, tracheo-esophageal fistula and high anorectal malformation are the major causes of mortality in early infancy and thus underline the importance of detailed investigation for the early recognition and optimal management. Those malformations which are not life threatening can be managed electively, keeping in mind the risks and benefits of surgery, available expertise and growth of the child. HFM is progressive in nature and early surgery is usually not undertaken, unless the deformity is severe and affects masticatory function(4). Previous studies show acceptable intelligence quotients and growth, even in infants with multiple manifestations(11).

The antenatal diagnosis of VACTERL can be suspected on ultrasonography early in the second trimester, especially if the fetus is severely affected. Important clues include polyhydramnios, small or absent stomach (esophageal-esophageal fistula with atresia), hemiverterbrae or scoliosis, limb defects, renal and cardiac defects(1). Termination of pregnancy can be offered if it is detected before the period of viability. Delivery in a tertiary center is required for prompt surgical repair and rehabilitation.

Contributors: PSSK was involved in patient care and review of literature. He also drafted the manuscript. SD supervized the patient care and critically reviewed the manuscript. AN supervized patient care and will act as guarantor for the article. KM managed the patient.

Funding: None.

Competing interests: None stated.

11. Bull MJ, Bryson CQ, Grosfeld J, Schreiner RL. VATER association: analysis of growth and development. Am J Perinatol 1985; 2: 35-38.