Acta Pzdiatr Scand 66: 783-785, 1977

CASE REPORT

MONOZYGOTIC TWINS CONCORDANT FOR TRACHEO-ESOPHAGEAL FISTULA AND DISCORDANT FOR THE VATER ASSOCIATION SUSANNE L. KING,' R. L. LADDA and S . J. SHOCHAT From the Departments of Pediatrics and Surgery the Pennsylvania State University, College of Medicine Hershey, Pennsylvania, USA

ABSTRACT. King, S. L., Ladda, R. L. and Shochat, S. J. (Departments of Pediatrics and Surgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA), Monozygotic twins concordant for tracheo-esophageal fistula and discordant for the VATER association. Acta Paediatr Scand, 66: 783, 1977.-Monozygotic female twins were concordant for tracheo-esophageal fistula (TEF); and one twin also manifested other anomalies of the VATER association, including agenesis of the female reproductive tract. Review of the literature discloses a familial tendency for recurrence of TEF and a high concordance rate in monozygotic twins, indicating a significant genetic influence for the isolated anomaly. In the case of the VATER association, the sporadic occurrence of affected individuals and discordance in twins implicates the effect of non-genetic factors. KEY WORDS: Tracheo-esophageal fistula, VATER association, monozygotic twins, female genitalia.

Tracheo-esophageal fistula (TEF) may occur as an isolated anomaly or associated with one or more defects. Quan & Smith (14) noted that certain of these anomalies occurred together more frequently than expected by chance alone, and they proposed the acronym VATER to denote the apparently non-random association of vertebral anomalies, anal atresia, TEF, and renal and/or radial dysplasia. More recently, malformations of the male external genitalia have been described as part of this association of anomalies (1). We wish to report a case of monozygotic female twins who were concordant for tracheo-esophageal fistula. One twin also exhibited anomalies characteristic of the VATER association, as well as agenesis of the female reproductive tract. A similar combination of malformations in twins has not been reported previously.

CASE REPORT Monozygotic female twins were born at approximately 32 weeks' gestation to a mother in good health. Zygosity of the twins was established by examination of the placenta; it had a single chorion and a single amnion. The pregnancy was complicated by polyhydramnios. Both twins were cyanotic at birth and required intubation and position pressure 02. Several hours after birth, the twins were found to have TEF, and they were transferred to our medical center for care. Twin A weighed 1360 g at birth; physical examination revealed no abnormalities. An X-ray study revealed a blind, upper esophageal pouch consistent with the diagnosis of TEF with esophageal atresia (Type C). Skeletal X-rays, intravenous pyelogram (IVP) and electrocardiogram (ECG) revealed no further abnormalities. Twin B weighed 1200 g and was noted to have an imperforate anus with a fistula to the vulvar area, and no vaginal orifice. X-ray study also revealed a blind esophageal pouch, confirming the diagnosis of TEF with Special Trainee in Medical Genetics; on leave from Northwestern University, School of Medicine, Fourth Year Class.

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esophageal atresia (Type C). Skeletal X-rays disclosed two left hemi-vertebrae and fusion of two pairs of ribs in the right thorax. IVP showed an ectopic midline pelvic kidney, with a single ureter. ECG was normal. This infant died after three months, and autopsy revealed agenesis of the fallopian tubes, uterus and vagina. The karyotype was normal.

DISCUSSION Six sets of twins concordant for TEF have been reported (4, 5 , 7, 11, 19). In five twins in which zygosity was determined, four were monozygotic and one set was dizygotic. Although isolated TEF generally has been a sporadic occurrence in an otherwise normal family, it has recurred in families, most often in the offspring of normal parents (8, 10, 17). Engel et al. (10) described TEF in a mother and her child, and Schimke et al. (17) found five members of one family affected. In contrast, individuals considered to have the VATER association (3 or more defects) have all occurred sporadically (1, 14, 18). In one family, TEF and imperforate anus occurred in three siblings of normal parents (12), but no other defects were noted. In only one other instance has the VATER association occurred in twins, and, as in our case, only one twin was affected (18). Thus, TEF is associated with a definite familial tendency, whereas the VATER association is not. Barry & Auldist ( 2 ) reported that 43% of their patients with TEF had at least one other major abnormality, the most frequently occurring being those of the VATER set of anomalies. They suggested that the VATER association should be considered as part of a spectrum that ranges from the occurrence of one defect alone, such as TEF, to the full set of VATER anomalies. However, instances of the VATER association have all been sporadic, and, with the exception of our monozygotic twins, we are unaware of the occurrence of isolated TEF and the VATER association in near relatives. On the other hand, isolated TEF is associated with a familial tendency. This suggests that the etiology of isolated TEF Acta Pzdiatr Scand 66

may differ from that of TEF occurring with the VATER association. Isolated TEF is estimated to occur from 1 in 800 to 1 in 2 500 live births (3, 13). The familial tendency for TEF (simulating autosomal recessive and dominant inheritance patterns), and the increased occurrence in near relatives (monozygotic twins, siblings, and offspring) compared to the general population, suggests a multifactorial mode of heritability ( 6 ) .Applying Edwards' (9) empiric formula ( fpopulation incidence), an estimate of the recurrence risk of TEF in first-degree relatives may range from 2-3.5%, i.e. 25-50 X greater risk than the general population. Because of this increased recurrence risk, with the economic and psychological burden associated with the surgical correction and long range treatment of TEF, prenatal diagnosis (amniography) may be offered in subsequent pregnancies.Contrast material injected into the amniotic fluid is swallowed by the fetus, outlining the gastrointestinal tract and permitting the diagnosis of TEF (15). The occurrence of genital anomalies with the VATER association is a recent observation (1, 18). Genital malformations noted by Apold et al. (1) in 3 of 7 male patients with the VATER association included bifid scrotum, dysplastic penis and hypospadius with testicular atrophy. They also called attention to earlier reports of hypospadius and female pseudohermaphroditism in other patients with the VATER set of anomalies (16, 18). In twin B, the female reproductive system was completely absent; not even the external vaginal orifice was present. The seventy of this defect in our patient suggests a total failure of Mullerian differentiation.

REFERENCES 1. Apold, J., Dahl, E. & Aarskog, D.: The VATER Association: Malformations of the male external genitalia. Acta Paediatr Scand, 65: 150, 1976. 2 . Barry, J. E. & Auldist, A. W.: The VATER Association: One end of a spectrum of anomalies. A m J Dis Child, 128:769, 1974.

Monozygotic tbt-t’ins 785 3 . Belsey, R. H. & Donnison, C. P.: Congenital atresia of the oesophagus. Br Med J , 11: 324, 1950. 4. Blank, R. H . , Prillaman, P. E. & Minor, G. R.: Congenital esophageal atresia with tracheoesophageal fistula occurring in identical twins. J Thoracic Cardiovusc Surg, 53: 192, 1967. 5 . Bolam, D., Severn, C. B., Ferlic, R. & Van Leeuwen, G.: Esophageal atresia with tracheoesophageal fistula in twins. Nebraska Med J , 58: 329, 1973. 6. Carter, C. 0.: Genetics of common single malformations. Br Med Bull, 32: 2 I , 1976. 7. David, T. J . & O’Callaghan, S. E.: Twinning and oesophageal atresia. Arch Dis Child, 49: 660, 1974. 8. Dennis, N. R., Nicholas, J. L. & Kovar, I.: Oesophageal atresia. Arch Dis Child, 48: 980, 1973. 9. Edwards, J . H.: The simulation of Mendelism. Acta Genet, 10: 63, 1960. 10. Engel, M. A,, Vos, L. J . M., deVries, J . A . & Kuijjer, P. J.: Esophageal atresia with tracheoesophageal fistula in mother and child. J Pediatr Surg, 5:564, 1970. I I . Farha, S . J., Diener, C. H. & Block, P. R.:Esophageal atresia in twins. J Kuns Med Soc, 72:386, 1971. 12. Forrester, R. M. & Cohen, S. J.: Esophageal atresia associated with an anorectal anomaly and probable laryngeal fissure in three siblings. J Pediatr Surg, 5 : 674, 1970. 13. Franklin, R. H.: Congenital atresia of the oesophagus. Lancet, 11: 243, 1947.

14. Quan, L. & Smith, D. W.: The VATER association. J Pediutr, 82: 104, 1973. IS. Queenan, J . T. & Gadow, E.: Amniography for detection of congenital malformations. Obstet Gynecol, 35: 648, 1970. 16. Say, B. & Gerald, P. S.: A new polydactylylimperforate-anuslvertebral-anomalies syndrome. Luncet, 11: 688, 1968. 17. Schimke, R. N., Leape, 1,. L. & Holder, T. M . : Familial occurrence of esophageal atresia: A preliminary report. Birth Defects: Original Article Series VIIl (2):22, 1972. 18. Temtamy, S. A. & Miller, J . D.: Extending the scope of the VATER association: Definition of the VATER syndrome. J Pediatr, 85: 345, 1974. 19. Woolley, M . M., Chinnock, R. F. & Paul, R . H.: Premature twins with esophageal atresia and tracheoesophageal fistula. Actu Puediatr Scand, 50: 423. 1961.

Submitted March 7, 1977 Accepted April 2 1. 1977

(R. L. L.) Department of Pediatrics Pennsylvania State University Hershey Pennsylvania 17033 USA

Ai.trr P z d i a t r Scritid b6

Monozygotic twins concordant for tracheo-esophageal fistula and discordant for the VATER association.

Acta Pzdiatr Scand 66: 783-785, 1977 CASE REPORT MONOZYGOTIC TWINS CONCORDANT FOR TRACHEO-ESOPHAGEAL FISTULA AND DISCORDANT FOR THE VATER ASSOCIATIO...
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