Bipolar Disorder in a Patient with VACTERL Syndrome: A Case Report

Parinda Parikh; Namitha Maria Mathew; Ananya Reddy Dadem; Sahia Manepalli; Rithika Narravula; Dilinuer Wubuli; Himani J Suthar; Shaurya Kumar Singh; Eunsaem Lee; Arushi Chandra-Kaushik; Avish Chandra; Ishant Buddhavarapu; Mahiya Buddhavarapu; Mina Oza

doi:10.23958/ijirms/vol10-i09/2116

Abstract

VACTERL association is a non-random constellation of congenital anomalies, typically involving at least three of the following systems: vertebral defects, anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies, and limb abnormalities. While defined by structural defects, emerging evidence suggests increased rates of correlations with neurodevelopmental and psychiatric conditions. Bipolar disorder is a chronic mood disorder marked by recurrent episodes of mania or hypomania and depression, with pathophysiology involving fronto-limbic dysregulation, neurotransmitter imbalance, neuroinflammation, mitochondrial dysfunction, and impaired neuroplasticity. We report a case of Bipolar I Disorder in a 21-year-old man with VACTERL association (vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula) and normal cognitive development. He presented with a two-week manic episode with psychotic features and responded well to lithium and olanzapine. To our knowledge, this is the first case reported a potential link between VACTERL association and a bipolar disorder. This case highlights the need for increased awareness of possible psychiatric comorbidities in patients with complex congenital anomalities and underscores the importance of incorporating neuropsychiatric screening into VACTERL patient care.

Keywords

VACTERLBipolar disorderNeuropsychiatric comorbiditySurgeryCase report

References

Solomon B. D. (2011). VACTERL/VATER Association. Orphanet journal of rare diseases, 6, 56. https://doi.org/10.1186/1750-1172-6-56DOI ↗Google Scholar ↗
Solomon, B. D., Baker, L. A., Bear, K. A., Cunningham, B. K., Giampietro, P. F., Hadigan, C., Hadley, D. W., Harrison, S., Levitt, M. A., Niforatos, N., Paul, S. M., Raggio, C., Reutter, H., & Warren-Mora, N. (2014). An approach to the identification of anomalies and etiologies in neonates with identified or suspected VACTERL (vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, cardiac anomalies, renal anomalies, and limb anomalies) association. The Journal of pediatrics, 164(3), 451–7.e1. https://doi.org/10.1016/j.jpeds.2013.10.086DOI ↗Google Scholar ↗
Kassa, A. M., & Lilja, H. E. (2023). Neurodevelopmental outcomes in individuals with VACTERL association. A population-based cohort study. PloS one, 18(6), e0288061. https://doi.org/10.1371/journal.pone.0288061DOI ↗Google Scholar ↗
McIntyre, R. S., Berk, M., Brietzke, E., Goldstein, B. I., López-Jaramillo, C., Kessing, L. V., Malhi, G. S., Nierenberg, A. A., Rosenblat, J. D., Majeed, A., Vieta, E., Vinberg, M., Young, A. H., & Mansur, R. B. (2020). Bipolar disorders. Lancet (London, England), 396(10265), 1841–1856. https://doi.org/10.1016/S0140-6736(20)31544-0DOI ↗Google Scholar ↗
Parikh, P., Wubuli, D., & Pansuriya, P., et al. (2025). New-onset bipolar with psychotic features in adolescence years after Chiari I malformation surgery: A case report and literature review. International Journal of Case Reports, 17, (06), 33763-33765.https://doi.org/10.24941/ijcr.49230.07.2025DOI ↗Google Scholar ↗
Jain A, Mitra P. Bipolar Disorder. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558998/Google Scholar ↗
World Health Organization. (2024). Bipolar disorder [Fact sheet]. https://www.who.int/news‑room/fact‑sheets/detail/bipolar‑disorderGoogle Scholar ↗
Schiweck, C., Arteaga-Henriquez, G., Aichholzer, M., Edwin Thanarajah, S., Vargas-Cáceres, S., Matura, S., Grimm, O., Haavik, J., Kittel-Schneider, S., Ramos-Quiroga, J. A., Faraone, S. V., & Reif, A. (2021). Comorbidity of ADHD and adult bipolar disorder: A systematic review and meta-analysis. Neuroscience and biobehavioral reviews, 124, 100–123. https://doi.org/10.1016/j.neubiorev.2021.01.017DOI ↗Google Scholar ↗
Dunalska, A., Rzeszutek, M., Dębowska, Z., & Bryńska, A. (2021). Comorbidity of bipolar disorder and autism spectrum disorder - review paper. Współwystępowanie choroby afektywnej dwubiegunowej i zaburzeń ze spektrum autyzmu – przegląd badań. Psychiatria polska, 55(6), 1421–1431. https://doi.org/10.12740/PP/OnlineFirst/122350DOI ↗Google Scholar ↗
Quan, L., & Smith, D. W. (1973). The VATER association. Vertebral defects, Anal atresia, T-E fistula with esophageal atresia, Radial and Renal dysplasia: a spectrum of associated defects. The Journal of pediatrics, 82(1), 104–107. https://doi.org/10.1016/s0022-3476(73)80024-1DOI ↗Google Scholar ↗
Stevenson, R. E., & Hunter, A. G. (2013). Considering the Embryopathogenesis of VACTERL Association. Molecular syndromology, 4(1-2), 7–15. https://doi.org/10.1159/000346192DOI ↗Google Scholar ↗
Sun, M., Zhao, Q., Yang, B., Liu, L., Zhou, C., Yao, X., Bu, J., Bian, J., Ge, S., Zhu, Z., & Liu, B. (2025). Molecular mechanism, diagnosis, and treatment of VACTERL association. Frontiers in pediatrics, 13, 1609624. https://doi.org/10.3389/fped.2025.1609624DOI ↗Google Scholar ↗
Ritter, J., Lisec, K., Klinner, M., Heinrich, M., von Schweinitz, D., Kappler, R., & Hubertus, J. (2023). Genetic Disruption of Cilia-Associated Signaling Pathways in Patients with VACTERL Association. Children (Basel, Switzerland), 10(5), 882. https://doi.org/10.3390/children10050882DOI ↗Google Scholar ↗
Loepke, A. W., & Soriano, S. G. (2008). An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesthesia and analgesia, 106(6), 1681–1707. https://doi.org/10.1213/ane.0b013e318167ad77DOI ↗Google Scholar ↗
Sprung, J., Flick, R. P., Katusic, S. K., Colligan, R. C., Barbaresi, W. J., Bojanić, K., Welch, T. L., Olson, M. D., Hanson, A. C., Schroeder, D. R., Wilder, R. T., & Warner, D. O. (2012). Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia. Mayo Clinic proceedings, 87(2), 120–129. https://doi.org/10.1016/j.mayocp.2011.11.008DOI ↗Google Scholar ↗
Dawson, S., Glasson, E. J., Dixon, G., & Bower, C. (2009). Birth defects in children with autism spectrum disorders: a population-based, nested case-control study. American journal of epidemiology, 169(11), 1296–1303. https://doi.org/10.1093/aje/kwp059DOI ↗Google Scholar ↗
Timonen-Soivio, L., Vanhala, R., Malm, H., Leivonen, S., Jokiranta, E., Hinkka-Yli-Salomäki, S., Gissler, M., Brown, A. S., & Sourander, A. (2015). The association between congenital anomalies and autism spectrum disorders in a Finnish national birth cohort. Developmental medicine and child neurology, 57(1), 75–80. https://doi.org/10.1111/dmcn.12581DOI ↗Google Scholar ↗
Magioncalda, P., & Martino, M. (2022). A unified model of the pathophysiology of bipolar disorder. Molecular psychiatry, 27(1), 202–211. https://doi.org/10.1038/s41380-021-01091-4DOI ↗Google Scholar ↗
Oliva V, Fico G, De Prisco M, Gonda X, Rosa AR, Vieta E. Bipolar disorders: an update on critical aspects. Lancet Reg Health Eur. 2024;48:101135. Published 2024 Nov 29. doi:10.1016/j.lanepe.2024.101135DOI ↗Google Scholar ↗
Frey, B. N., Andreazza, A. C., Nery, F. G., Martins, M. R., Quevedo, J., Soares, J. C., & Kapczinski, F. (2007). The role of hippocampus in the pathophysiology of bipolar disorder. Behavioural pharmacology, 18(5-6), 419–430. https://doi.org/10.1097/FBP.0b013e3282df3cdeDOI ↗Google Scholar ↗

[refR-1] Solomon B. D. (2011). VACTERL/VATER Association. Orphanet journal of rare diseases, 6, 56. https://doi.org/10.1186/1750-1172-6-56DOI ↗Google Scholar ↗

[refR-2] Solomon, B. D., Baker, L. A., Bear, K. A., Cunningham, B. K., Giampietro, P. F., Hadigan, C., Hadley, D. W., Harrison, S., Levitt, M. A., Niforatos, N., Paul, S. M., Raggio, C., Reutter, H., & Warren-Mora, N. (2014). An approach to the identification of anomalies and etiologies in neonates with identified or suspected VACTERL (vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, cardiac anomalies, renal anomalies, and limb anomalies) association. The Journal of pediatrics, 164(3), 451–7.e1. https://doi.org/10.1016/j.jpeds.2013.10.086DOI ↗Google Scholar ↗

[refR-3] Kassa, A. M., & Lilja, H. E. (2023). Neurodevelopmental outcomes in individuals with VACTERL association. A population-based cohort study. PloS one, 18(6), e0288061. https://doi.org/10.1371/journal.pone.0288061DOI ↗Google Scholar ↗

[refR-4] McIntyre, R. S., Berk, M., Brietzke, E., Goldstein, B. I., López-Jaramillo, C., Kessing, L. V., Malhi, G. S., Nierenberg, A. A., Rosenblat, J. D., Majeed, A., Vieta, E., Vinberg, M., Young, A. H., & Mansur, R. B. (2020). Bipolar disorders. Lancet (London, England), 396(10265), 1841–1856. https://doi.org/10.1016/S0140-6736(20)31544-0DOI ↗Google Scholar ↗

[refR-5] Parikh, P., Wubuli, D., & Pansuriya, P., et al. (2025). New-onset bipolar with psychotic features in adolescence years after Chiari I malformation surgery: A case report and literature review. International Journal of Case Reports, 17, (06), 33763-33765.https://doi.org/10.24941/ijcr.49230.07.2025DOI ↗Google Scholar ↗

[refR-6] Jain A, Mitra P. Bipolar Disorder. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558998/Google Scholar ↗

[refR-7] World Health Organization. (2024). Bipolar disorder [Fact sheet]. https://www.who.int/news‑room/fact‑sheets/detail/bipolar‑disorderGoogle Scholar ↗

[refR-8] Schiweck, C., Arteaga-Henriquez, G., Aichholzer, M., Edwin Thanarajah, S., Vargas-Cáceres, S., Matura, S., Grimm, O., Haavik, J., Kittel-Schneider, S., Ramos-Quiroga, J. A., Faraone, S. V., & Reif, A. (2021). Comorbidity of ADHD and adult bipolar disorder: A systematic review and meta-analysis. Neuroscience and biobehavioral reviews, 124, 100–123. https://doi.org/10.1016/j.neubiorev.2021.01.017DOI ↗Google Scholar ↗

[refR-9] Dunalska, A., Rzeszutek, M., Dębowska, Z., & Bryńska, A. (2021). Comorbidity of bipolar disorder and autism spectrum disorder - review paper. Współwystępowanie choroby afektywnej dwubiegunowej i zaburzeń ze spektrum autyzmu – przegląd badań. Psychiatria polska, 55(6), 1421–1431. https://doi.org/10.12740/PP/OnlineFirst/122350DOI ↗Google Scholar ↗

[refR-10] Quan, L., & Smith, D. W. (1973). The VATER association. Vertebral defects, Anal atresia, T-E fistula with esophageal atresia, Radial and Renal dysplasia: a spectrum of associated defects. The Journal of pediatrics, 82(1), 104–107. https://doi.org/10.1016/s0022-3476(73)80024-1DOI ↗Google Scholar ↗

[refR-11] Stevenson, R. E., & Hunter, A. G. (2013). Considering the Embryopathogenesis of VACTERL Association. Molecular syndromology, 4(1-2), 7–15. https://doi.org/10.1159/000346192DOI ↗Google Scholar ↗

[refR-12] Sun, M., Zhao, Q., Yang, B., Liu, L., Zhou, C., Yao, X., Bu, J., Bian, J., Ge, S., Zhu, Z., & Liu, B. (2025). Molecular mechanism, diagnosis, and treatment of VACTERL association. Frontiers in pediatrics, 13, 1609624. https://doi.org/10.3389/fped.2025.1609624DOI ↗Google Scholar ↗

[refR-13] Ritter, J., Lisec, K., Klinner, M., Heinrich, M., von Schweinitz, D., Kappler, R., & Hubertus, J. (2023). Genetic Disruption of Cilia-Associated Signaling Pathways in Patients with VACTERL Association. Children (Basel, Switzerland), 10(5), 882. https://doi.org/10.3390/children10050882DOI ↗Google Scholar ↗

[refR-14] Loepke, A. W., & Soriano, S. G. (2008). An assessment of the effects of general anesthetics on developing brain structure and neurocognitive function. Anesthesia and analgesia, 106(6), 1681–1707. https://doi.org/10.1213/ane.0b013e318167ad77DOI ↗Google Scholar ↗

[refR-15] Sprung, J., Flick, R. P., Katusic, S. K., Colligan, R. C., Barbaresi, W. J., Bojanić, K., Welch, T. L., Olson, M. D., Hanson, A. C., Schroeder, D. R., Wilder, R. T., & Warner, D. O. (2012). Attention-deficit/hyperactivity disorder after early exposure to procedures requiring general anesthesia. Mayo Clinic proceedings, 87(2), 120–129. https://doi.org/10.1016/j.mayocp.2011.11.008DOI ↗Google Scholar ↗

[refR-16] Dawson, S., Glasson, E. J., Dixon, G., & Bower, C. (2009). Birth defects in children with autism spectrum disorders: a population-based, nested case-control study. American journal of epidemiology, 169(11), 1296–1303. https://doi.org/10.1093/aje/kwp059DOI ↗Google Scholar ↗

[refR-17] Timonen-Soivio, L., Vanhala, R., Malm, H., Leivonen, S., Jokiranta, E., Hinkka-Yli-Salomäki, S., Gissler, M., Brown, A. S., & Sourander, A. (2015). The association between congenital anomalies and autism spectrum disorders in a Finnish national birth cohort. Developmental medicine and child neurology, 57(1), 75–80. https://doi.org/10.1111/dmcn.12581DOI ↗Google Scholar ↗

[refR-18] Magioncalda, P., & Martino, M. (2022). A unified model of the pathophysiology of bipolar disorder. Molecular psychiatry, 27(1), 202–211. https://doi.org/10.1038/s41380-021-01091-4DOI ↗Google Scholar ↗

[refR-19] Oliva V, Fico G, De Prisco M, Gonda X, Rosa AR, Vieta E. Bipolar disorders: an update on critical aspects. Lancet Reg Health Eur. 2024;48:101135. Published 2024 Nov 29. doi:10.1016/j.lanepe.2024.101135DOI ↗Google Scholar ↗

[refR-20] Frey, B. N., Andreazza, A. C., Nery, F. G., Martins, M. R., Quevedo, J., Soares, J. C., & Kapczinski, F. (2007). The role of hippocampus in the pathophysiology of bipolar disorder. Behavioural pharmacology, 18(5-6), 419–430. https://doi.org/10.1097/FBP.0b013e3282df3cdeDOI ↗Google Scholar ↗