VACTERL Associated with a Rare Limb Anomaly Combined with Edward (Trisomy 18) Syndrome

Abstract

VACTERL association is a heterogeneous condition that includes at least three out of six core structural defects which occur together more commonly than would be expected by chance alone. We report a rare association of VACTERL with unilateral proximal focal femoral deficiency and trisomy 18 syndrome.

INTRODUCTION

VACTERL association is a heterogeneous condition that includes at least three out of six core structural defects (Vertebral, Anal, cardiac, Tracheo-esophageal fistula, Renal, and Limb anomalies) which occur together more commonly than would be expected by chance alone. Previously, VACTERL had been seen to be associated with trisomy 13, trisomy 21, Mullerian aplasia syndrome, and Chiari malformation. Khoury et al. were the first to report VACTERL association combined with trisomy 18 syndrome.[1] In 2014, Kim et al. reported a case of VACTERL association with meningomyelocele combined with trisomy 18 syndrome.[2] We report a case of VACTERL associated with unilateral proximal focal femoral deficiency (PFFD) and trisomy 18. This is a rare case of VACTERL combined with PFFD combined with trisomy of chromosome 18.

CASE REPORT

A 2-day-old male neonate weighing 2.8 kg born to a 38-year-old primigravida presented to us with absent anal opening and short right lower limb. He was born by spontaneous vaginal delivery. There was no significant history of antenatal insult to the baby. There was neither any history of maternal diabetes and consanguinity nor any history of major congenital anomaly in other family member. On examination, the patient had narrow eyelid folds, widely spaced eyes, and rocker bottom feet. The abdomen was asymmetrically distended toward the left side. The anus was absent, and midline perineal raphe were poorly developed. The right lower limb was short in comparison to the left. X-ray spine showed kyphoscoliosis and absent of the right femur bone and the distal segment of femur overriding the right iliac bone [Figure 1a and b]. His routine blood investigations were within normal limits. Prone cross-table X-ray in lateral position revealed high-type anorectal malformation (ARM). Echocardiography showed atrial septal defect (osteum secundum 1.8 mm) which resolved in the subsequent visit. Ultrasound of the abdomen showed no abnormality. High sigmoid colostomy was done. The postoperative period was uneventful. High-resolution chromosome analysis showed Trypsin- Giemsa G-band (GTG) banding with 47 xy + 18 karyotype in proband [Figure 2a and b]. Distal cologram done after 3 months showed high rectoprostatic fistula. Subsequently, abdomino-perineal pull through was done. The patient had perineal excoriation due to frequent fecal soiling which was managed by rectal wash and topical zinc oxide-based cream. The patient is now 2 year old and comes for regular follow-up. For the right lower limb anomaly, surgical treatment has been planned as resection of the proximal part of dysplastic femur and rotation arthroplasty of the residual limb along with femoropelvic arthrodesis by 3 years of age. The patient is presently under orthopedic rehabilitation for the lower limb.

Figure 1.

(a) Deficiency of the right femur and hypoplasia of the right ilium, (b) arrow showing distal part of the femur overlapping the iliac bone

Figure 2.

(a) Clinical photograph of the patient, (b) picture of the chromosome analysis

DISCUSSION

The term “VACTERL” describes a group of anomalies, which was first described by Quan and Smith initially as the acronym VATER and later it was expanded to VACTERL that included limb malformations. The incidence of VACTERL anomaly is approximately 1 in 10,000–1 in 40,000 live-born infants.

The VACTERL association is diverse in etiology, and various mutations in homeobox D13, phosphatase and tensin homolog, zic family member 3, and interstitial deletions of chromosome 17 (del (17) (q22q23.3) have been reported previously.[3] In our patient, the high-resolution GTC banding chromosomal analysis was reported to be normal other than trisomy 18. Approximately 50% of infants with trisomy 18 syndrome live <1 week, and approximately 5%–10% of infants survive beyond the 1^st year, who are mostly mosaic trisomy or partial trisomy.[4]

Limb malformations have been reported in approximately 40%–50% of patients of VACTERL syndrome, mostly as preaxial. It includes a displaced or hypoplastic thumb, extra digits (polydactyly), fusion of digits (syndactyly), and forearm defects such as radial aplasia. The lower limb anomalies commonly seen in the patients of ARM are foot and toe anomalies and congenital hip dislocation. In 2005, Ratan et al. reported a case of VACTERL with right lower limb shortening due to PFFD with absent fibula.[5] This was contrary to the series of cases they had reported earlier. However, they were unable to carry out the chromosomal analysis as the baby succumbed to congestive cardiac failure. Our case had right lower limb shortening due to PFFD. The fibula was present. In addition, there was rocker bottom foot classically seen in Edward (trisomy 18) syndrome.

In conclusion, a patient of ARM with VACTERL associated with PFFD combined with trisomy 18 (Edward syndrome) has been described. Chromosomal analysis helps in elucidating the genetic abnormality in these cases and is imperative for genetic counseling.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.