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Spinal dysraphism as a new entity in V.A.C.TE.R.L syndrome, resulting in a novel acronym V.A.C.TE.R.L.S

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Abstract

Anorectal malformation (ARM) is the most common symptom in VACTERL syndrome (vertebral, anal, cardiac, tracheo-esophageal fistula, renal, and limb anomalies). The association of ARM and spinal dysraphisms (DYS) is well documented. We aim to better evaluate children with VACTERL association and ARM, considering the presence or not of DYS. Between 2000 and 2015, 279 children with VACTERL associations were identified in Necker Children’s Hospital, Paris. We identified 61 VACTERL children (22%) with ARM. A total of 52 VACTERL children with ARM were included. DYS were identified in 36/52 of cases (69.2%). A total of 33 (63.5%) VACTERL children presented with sphincterial dysfunction. We constated that 28/33 (84.8%) of them had DYS + (p < 0.0001). More children in ARM (DYS +) subgroup are presenting with initial urinary sphincter dysfunction (58 vs 19%, p < 0.009) than ARM (DYS -). We identified 29 lipoma filum in our series, which were not statistically associated with urinary disorders (p = 0.143).

Conclusion: We propose to refine the definition of VACTERL association, by adding S as Spinal defect to include it as an integral part of this syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.

What is Known:

• The VACTERL association: congenital anomalies of the bony vertebral column (V), anorectal malformation (A), congenital cardiopathy (C), tracheo-esophageal defects (TE), renal and urinary tract anomalies (R), and limb malformations (L).

• VACTERL children needs a complete appraisal, as early as possible, to adopt the most appropriate therapeutic management.

What is New:

• Include spine dysraphism (DYS) as a part of this syndrome, resulting in a novel acronym V.A.C.TE.R.L.S.

• The significant correlation between VACTERL/DYS and urinary dysfunction requires to investigate the spine cord prenatally.

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Abbreviations

ARM:

Anorectal malformation

ART:

Assisted reproductive techniques

DYS:

Dysraphism

IVF:

In vitro fertilization

MRI:

Magnetic resonance imaging

VACTERL:

Vertebral (V), anorectal malformation (A), congenital cardiopathy (C), tracheo-esophageal defects (TE), renal and urinary tract anomalies (R), and limb malformations (L)

References

  1. Quan L, Smith DW (1973) The VATER association. Vertebral defects, anal atresia, T-E fistula with esophageal atresia, radial and renal dysplasia: a spectrum of associated defects. J Pediatr 82:104–107

    Article  CAS  Google Scholar 

  2. Temtamy SA, Miller JD (1974) Extending the scope of the VATER association: definition of the VATER syndrome. J Pediatr 85:345–349

    Article  CAS  Google Scholar 

  3. Usami K, Lallemant P, Roujeau T, James S, Beccaria K, Levy R, Rocco F, Sainte-Rose C, Zerah M (2016) Spinal lipoma of the filum terminale: review of 174 consecutive patients. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg 32:1265–1272. https://doi.org/10.1007/s00381-016-3072-8

    Article  Google Scholar 

  4. Kuo M-F, Tsai Y, Hsu W-M, Chen RS, Tu YK, Wang HS (2007) Tethered spinal cord and VACTERL association. J Neurosurg 106:201–204. https://doi.org/10.3171/ped.2007.106.3.201

    Article  PubMed  Google Scholar 

  5. Sewell MJ, Chiu YE, Drolet BA (2015) Neural tube dysraphism: review of cutaneous markers and imaging. Pediatr Dermatol 32:161–170. https://doi.org/10.1111/pde.12485

    Article  PubMed  Google Scholar 

  6. Keckler SJ, St Peter SD, Valusek PA, Tsao K, Snyder CL, Holcomb GW 3rd, Ostlie DJ (2007) VACTERL anomalies in patients with esophageal atresia: an updated delineation of the spectrum and review of the literature. Pediatr Surg Int 23:309–313. https://doi.org/10.1007/s00383-007-1891-0

    Article  PubMed  Google Scholar 

  7. Stoll C, Alembik Y, Dott B, Roth MP (2007) Associated malformations in patients with anorectal anomalies. Eur J Med Genet 50:281–290. https://doi.org/10.1016/j.ejmg.2007.04.002

    Article  CAS  PubMed  Google Scholar 

  8. Levitt MA, Patel M, Rodriguez G, Gaylin DS, Pena A (1997) The tethered spinal cord in patients with anorectal malformations. J Pediatr Surg 32:462–468

    Article  CAS  Google Scholar 

  9. Rivosecchi M, Lucchetti MC, Zaccara A, de Gennaro M, Fariello G (1995) Spinal dysraphism detected by magnetic resonance imaging in patients with anorectal anomalies: incidence and clinical significance. J Pediatr Surg 30:488–490

    Article  CAS  Google Scholar 

  10. Valentini LG, Selvaggio G, Erbetta A et al (2013) Occult spinal dysraphism: lessons learned by retrospective analysis of 149 surgical cases about natural history, surgical indications, urodynamic testing, and intraoperative neurophysiological monitoring. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg 29:1657–1669. https://doi.org/10.1007/s00381-013-2186-5

    Article  Google Scholar 

  11. Al-Omari MH, Eloqayli HM, Qudseih HM, Al-Shinag MK (2011) Isolated lipoma of filum terminale in adults: MRI findings and clinical correlation. J Med Imaging Radiat Oncol 55:286–290. https://doi.org/10.1111/j.1754-9485.2011.02266.x

    Article  PubMed  Google Scholar 

  12. Garcelon N, Neuraz A, Benoit V, Salomon R, Kracker S, Suarez F, Bahi-Buisson N, Hadj-Rabia S, Fischer A, Munnich A, Burgun A (2017) Finding patients using similarity measures in a rare diseases-oriented clinical data warehouse: Dr. Warehouse and the needle in the needle stack. J Biomed Inform 73:51–61. https://doi.org/10.1016/j.jbi.2017.07.016

    Article  PubMed  Google Scholar 

  13. Bai Y, Yuan Z, Wang W, Zhao Y, Wang H, Wang W (2000) Quality of life for children with fecal incontinence after surgically corrected anorectal malformation. J Pediatr Surg 35:462–464. https://doi.org/10.1016/s0022-3468(00)90215-x

    Article  CAS  PubMed  Google Scholar 

  14. Oral A, Caner I, Yigiter M et al (2012) Clinical characteristics of neonates with VACTERL association. Pediatr Int Off J Jpn Pediatr Soc 54:361–364. https://doi.org/10.1111/j.1442-200X.2012.03566.x

    Article  Google Scholar 

  15. Midrio P, Nogare CD, Di Gianantonio E, Clementi M (2006) Are congenital anorectal malformations more frequent in newborns conceived with assisted reproductive techniques? Reprod Toxicol Elmsford N 22:576–577. https://doi.org/10.1016/j.reprotox.2006.05.004

    Article  CAS  Google Scholar 

  16. Davies MJ, Moore VM, Willson KJ, van Essen P, Priest K, Scott H, Haan EA, Chan A (2012) Reproductive technologies and the risk of birth defects. N Engl J Med 366:1803–1813. https://doi.org/10.1056/NEJMoa1008095

    Article  CAS  PubMed  Google Scholar 

  17. Bond-Taylor W, Starer F, Atwell JD (1973) Vertebral anomalies associated with esophageal atresia and tracheoesophageal fistula with reference to the initial operative mortality. J Pediatr Surg 8:9–13

    Article  CAS  Google Scholar 

  18. Stevenson RE (1974) The association of extra vertebras and tracheoesophageal anomalies. Birth Defects Orig Artic Ser 10:147–148

    CAS  PubMed  Google Scholar 

  19. Louhimo I, Lindahl H (1983) Esophageal atresia: primary results of 500 consecutively treated patients. J Pediatr Surg 18:217–229

    Article  CAS  Google Scholar 

  20. German JC, Mahour GH, Woolley MM (1976) Esophageal atresia and associated anomalies. J Pediatr Surg 11:299–306

    Article  CAS  Google Scholar 

  21. Ein SH, Palder SB, Filler RM (2006) Babies with esophageal and duodenal atresia: a 30-year review of a multifaceted problem. J Pediatr Surg 41:530–532. https://doi.org/10.1016/j.jpedsurg.2005.11.061

    Article  PubMed  Google Scholar 

  22. Driver CP, Shankar KR, Jones MO, Lamont GA, Turnock RR, Lloyd DA, Losty PD (2001) Phenotypic presentation and outcome of esophageal atresia in the era of the Spitz classification. J Pediatr Surg 36:1419–1421. https://doi.org/10.1053/jpsu.2001.26389

    Article  CAS  PubMed  Google Scholar 

  23. Yang C-F, Soong W-J, Jeng M-J, Chen SJ, Lee YS, Tsao PC, Hwang B, Wei CF, Chin TW, Liu C (2006) Esophageal atresia with tracheoesophageal fistula: ten years of experience in an institute. J Chin Med Assoc JCMA 69:317–321. https://doi.org/10.1016/S1726-4901(09)70265-5

    Article  PubMed  Google Scholar 

  24. Uehling DT, Gilbert E, Chesney R (1983) Urologic implications of the VATER association. J Urol 129:352–354

    Article  CAS  Google Scholar 

  25. Davidoff AM, Thompson CV, Grimm JM, Shorter NA, Filston HC, Oakes WJ (1991) Occult spinal dysraphism in patients with anal agenesis. J Pediatr Surg 26:1001–1005

    Article  CAS  Google Scholar 

  26. Muller CO, Crétolle C, Blanc T, Alova I, Jais JP, Lortat-Jacob S, Aigrain Y, Zérah M, Sarnacki S (2014) Impact of spinal dysraphism on urinary and faecal prognosis in 25 cases of cloacal malformation. J Pediatr Urol 10:1199–1205. https://doi.org/10.1016/j.jpurol.2014.05.012

    Article  PubMed  Google Scholar 

  27. Cho S, Moore SP, Fangman T (2001) One hundred three consecutive patients with anorectal malformations and their associated anomalies. Arch Pediatr Adolesc Med 155:587–591

    Article  CAS  Google Scholar 

  28. Tortori-Donati P, Rossi A, Cama A (2000) Spinal dysraphism: a review of neuroradiological features with embryological correlations and proposal for a new classification. Neuroradiology 42:471–491

    Article  CAS  Google Scholar 

  29. Carson JA, Barnes PD, Tunell WP, Smith EI, Jolley SG (1984) Imperforate anus: the neurologic implication of sacral abnormalities. J Pediatr Surg 19:838–842

    Article  CAS  Google Scholar 

  30. Walton M, Bass J, Soucy P (1995) Tethered cord with anorectal malformation, sacral anomalies and presacral masses: an under-recognized association. Eur J Pediatr Surg Off J Austrian Assoc Pediatr Surg Al Z Kinderchir 5:59–62. https://doi.org/10.1055/s-2008-1066168

    Article  CAS  Google Scholar 

  31. Totonelli G, Morini F, Catania VD, Schingo PM, Mosiello G, Palma P, Iacobelli BD, Bagolan P (2016) Anorectal malformations associated spinal cord anomalies. Pediatr Surg Int 32:729–735. https://doi.org/10.1007/s00383-016-3914-1

    Article  PubMed  Google Scholar 

  32. O’Neill BR, Yu AK, Tyler-Kabara EC (2010) Prevalence of tethered spinal cord in infants with VACTERL. J Neurosurg Pediatr 6:177–182. https://doi.org/10.3171/2010.5.PEDS09428

    Article  PubMed  Google Scholar 

  33. Koo B-N, Hong J-Y, Song H-T, Kim JM, Kil HK (2012) Ultrasonography reveals a high prevalence of lower spinal dysraphism in children with urogenital anomalies. Acta Anaesthesiol Scand 56:624–628. https://doi.org/10.1111/j.1399-6576.2011.02612.x

    Article  PubMed  Google Scholar 

  34. Hajnovic L, Trnka J (2007) Tethered spinal cord syndrome--the importance of time for outcomes. Eur J Pediatr Surg Off J Austrian Assoc Pediatr Surg Al Z Kinderchir 17:190–193. https://doi.org/10.1055/s-2007-965133

    Article  CAS  Google Scholar 

  35. Steinbok P, Garton HJL, Gupta N (2006) Occult tethered cord syndrome: a survey of practice patterns. J Neurosurg 104:309–313. https://doi.org/10.3171/ped.2006.104.5.309

    Article  PubMed  Google Scholar 

  36. Selden NR (2006) Occult tethered cord syndrome: the case for surgery. J Neurosurg 104:302–304. https://doi.org/10.3171/ped.2006.104.5.302

    Article  PubMed  Google Scholar 

  37. Drake JM (2006) Occult tethered cord syndrome: not an indication for surgery. J Neurosurg 104:305–308. https://doi.org/10.3171/ped.2006.104.5.305

    Article  PubMed  Google Scholar 

  38. Hilger A, Schramm C, Draaken M, Mughal SS, Dworschak G, Bartels E, Hoffmann P, Nöthen MM, Reutter H, Ludwig M (2012) Familial occurrence of the VATER/VACTERL association. Pediatr Surg Int 28:725–729. https://doi.org/10.1007/s00383-012-3073-y

    Article  PubMed  Google Scholar 

  39. Solomon BD (2018) The etiology of VACTERL association: current knowledge and hypotheses. Am J Med Genet C Semin Med Genet 178:440–446. https://doi.org/10.1002/ajmg.c.31664

    Article  PubMed  Google Scholar 

  40. Bartels E, Schulz AC, Mora NW, Pineda-Alvarez DE, Wijers CH, Marcelis CM, Stressig R, Ritgen J, Schmiedeke E, Mattheisen M, Draaken M, Hoffmann P, Hilger AC, Dworschak GC, Baudisch F, Ludwig M, Bagci S, Müller A, Gembruch U, Geipel A, Berg C, Bartmann P, Nöthen MM, van Rooij I, Solomon BD, Reutter HM (2012) VATER/VACTERL association: identification of seven new twin pairs, a systematic review of the literature, and a classical twin analysis. Clin Dysmorphol 21:191–195. https://doi.org/10.1097/MCD.0b013e328358243c

    Article  PubMed  PubMed Central  Google Scholar 

  41. Brosens E, Ploeg M, van Bever Y et al (2014) Clinical and etiological heterogeneity in patients with tracheo-esophageal malformations and associated anomalies. Eur J Med Genet 57:440–452. https://doi.org/10.1016/j.ejmg.2014.05.009

    Article  PubMed  Google Scholar 

  42. Reutter H, Hilger AC, Hildebrandt F, Ludwig M (2016) Underlying genetic factors of the VATER/VACTERL association with special emphasis on the “renal” phenotype. Pediatr Nephrol Berl Ger 31:2025–2033. https://doi.org/10.1007/s00467-016-3335-3

    Article  Google Scholar 

  43. Chen Y, Liu Z, Chen J, Zuo Y, Liu S, Chen W, Liu G, Qiu G, Giampietro PF, Wu N, Wu Z (2016) The genetic landscape and clinical implications of vertebral anomalies in VACTERL association. J Med Genet 53:431–437. https://doi.org/10.1136/jmedgenet-2015-103554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Catala M (2002) Genetic control of caudal development. Clin Genet 61:89–96

    Article  CAS  Google Scholar 

  45. Kim PC, Mo R, Hui Cc C (2001) Murine models of VACTERL syndrome: role of sonic hedgehog signaling pathway. J Pediatr Surg 36:381–384

    Article  CAS  Google Scholar 

  46. Lambert RD (2003) Safety issues in assisted reproductive technology: aetiology of health problems in singleton ART babies. Hum Reprod Oxf Engl 18:1987–1991. https://doi.org/10.1093/humrep/deg361

    Article  Google Scholar 

  47. Hansen M, Bower C, Milne E et al (2005) Assisted reproductive technologies and the risk of birth defects--a systematic review. Hum Reprod Oxf Engl 20:328–338. https://doi.org/10.1093/humrep/deh593

    Article  Google Scholar 

  48. Källén B, Finnström O, Nygren K-G, Olausson PO (2005) In vitro fertilization (IVF) in Sweden: infant outcome after different IVF fertilization methods. Fertil Steril 84:611–617. https://doi.org/10.1016/j.fertnstert.2005.02.038

    Article  PubMed  Google Scholar 

  49. Bonduelle M, Wennerholm U-B, Loft A et al (2005) A multi-Centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod Oxf Engl 20:413–419. https://doi.org/10.1093/humrep/deh592

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Pr Paul Chumas from Leeds for his proofreading of this study.

Author information

Authors and Affiliations

  1. Department of Pediatric Neurosurgery, Necker-EM Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France

    Aymeric Amelot, Timothée de Saint Denis & Michel Zerah

  2. Department of Visceral Pediatric surgery, Necker-EM Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France

    Célia Cretolle & Sabine Sarnacki

  3. Reference center for AnoRectal and rare Pelvic anomalies MAREP, Necker-EM Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France

    Célia Cretolle & Sabine Sarnacki

  4. cUMR7622 UPMC et CNRS, Paris cedex 05, France; dFédération de Neurologie, Groupe Hospitalier Pitié-Salpêtrière 47-83 boulevard de l’Hôpital, Paris Cedex 13, France

    Martin Catala

  5. Reference center for Chiari and Malformations of the Spine and the Spinal Cord C-MAVEM and Institute for Genetic Diseases IMAGINE , Necker-EM Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris-Descartes, Paris, France

    Michel Zerah

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Contributions

Aymeric Amelot: Dr. Amelot conceptualized and designed the study, carried out the initial analyses, drafted the initial manuscript, and approved the final manuscript as submitted.

Timothée de Saint Denis: Dr. de Saint Denis reviewed and revised the manuscript and approved the final manuscript as submitted.

Célia Cretolle: Dr. Cretolle coordinated and supervised data collection, critically reviewed the manuscript, and approved the final manuscript as submitted.

Sabine Sarnacki: Pr Sarnacki drafted the initial manuscript, reviewed the manuscript, and approved the final manuscript as submitted.

Martin Catala; Pr Catala drafted the initial manuscript, reviewed the manuscript, and approved the final manuscript as submitted.

Michel Zerah: Pr Zerah has operated and followed all the dysraphic patients and drafted the initial manuscript, reviewed the manuscript, and approved the final manuscript as submitted.

All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Aymeric Amelot.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Communicated by Piet Leroy

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Amelot, A., Cretolle, C., de Saint Denis, T. et al. Spinal dysraphism as a new entity in V.A.C.TE.R.L syndrome, resulting in a novel acronym V.A.C.TE.R.L.S. Eur J Pediatr 179, 1121–1129 (2020). https://doi.org/10.1007/s00431-020-03609-4

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