Skip to main content
SpringerLink
Log in

Lynch syndrome-associated repeated stroke with MLH1 frame-shift mutation

  • Quiz Cases
  • Published:
Neurological Sciences Aims and scope Submit manuscript

A Correction to this article was published on 02 February 2021

This article has been updated

Abstract

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms. Previous studies showed that MLH1, MSH2, MSH6, and PMS2 mutation in LS were associated with an elevated risk of colorectal, gastric, endometria, ovarian, and other cancers among family members. Patients of these kinds of cancers had high incidence of synchronous and metasynchronus. We describe the case of a 34-year-old female patient with 50 days of sudden dizziness and left limb weakness, whose head CT scan showed large infarction in the right frontal temporal parietal lobe and basal ganglia area. Imaging examinations and pathological biopsy indicated high-grade serous carcinoma (HGSC) IIIA1 of the right ovary. In addition, a novel frame-shift mutation in the MLH1 gene (c.1621dupG, p.A541Gfs*16) was found in the genetic panel sequence. It may render declining of MLH1 protein and also associate with the patient’s progressive clinical manifestations of multiple systems. Therefore, the timely use of prenatal diagnosis to prevent unnecessary new cases of this severe genetic disease is available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Change history

References

  1. Biller LH, Syngal S, Yurgelun MB (2019) Recent advances in lynch syndrome. Familial Cancer 18(2):211–219

    Article  CAS  Google Scholar 

  2. Cox VL, Saeed Bamashmos AA, Foo WC, Gupta S, Yedururi S, Garg N, Kang HC (2018) Lynch syndrome: genomics update and imaging review. Radiographics 38(2):483–499

    Article  Google Scholar 

  3. Yurgelun MB, Hampel H (2018) Recent advances in lynch syndrome: diagnosis, treatment, and cancer prevention. Am Soc Clin Oncol Educ Book 38:101–109

    Article  Google Scholar 

  4. Carethers JM, Stoffel EM (2015) Lynch syndrome and Lynch syndrome mimics: the growing complex landscape of hereditary colon cancer. World J Gastroenterol 21(31):9253–9261

    Article  CAS  Google Scholar 

  5. Pellat A, Netter J, Perkins G, Cohen R, Coulet F, Parc Y, Svrcek M, Duval A, André T (2019) Lynch syndrome: what is new? Bull Cancer 106(7–8):647–655

    Article  Google Scholar 

  6. Castro-Mujica MDC, Barletta-Carrillo C (2018) Lynch syndrome: genetic, clinical and diagnostic aspects. Rev Gastroenterol Peru 38(3):265–279

    PubMed  Google Scholar 

  7. Ahadova A, Gallon R, Gebert J, Ballhausen A, Endris V, Kirchner M, Stenzinger A, Burn J, von Knebel Doeberitz M, Bläker H, Kloor M (2018) Three molecular pathways model colorectal carcinogenesis in Lynch syndrome. Int J Cancer 143(1):139–150

    Article  CAS  Google Scholar 

  8. Menahem B, Alves A, Regimbeau JM, Sabbagh C (2019) Lynch syndrome: current management in 2019. J Visc Surg 156(6):507–514

    Article  CAS  Google Scholar 

  9. Patil NR, Khan GN (2020) Exceptional response to a single cycle of immunotherapy in a Lynch syndrome patient with metastatic pancreatic adenocarcinoma. Am J Case Rep 21:e923803

    Article  Google Scholar 

  10. Latham A, Srinivasan P, Kemel Y, Shia J, Bandlamudi C, Mandelker D, Middha S, Hechtman J, Zehir A, Dubard-Gault M, Tran C, Stewart C, Sheehan M, Penson A, DeLair D, Yaeger R, Vijai J, Mukherjee S, Galle J, Dickson MA, Janjigian Y, O’Reilly EM, Segal N, Saltz LB, Reidy-Lagunes D, Varghese AM, Bajorin D, Carlo MI, Cadoo K, Walsh MF, Weiser M, Aguilar JG, Klimstra DS, Diaz LA Jr, Baselga J, Zhang L, Ladanyi M, Hyman DM, Solit DB, Robson ME, Taylor BS, Offit K, Berger MF, Stadler ZK (2019 Feb 1) Microsatellite instability is associated with the presence of Lynch syndrome pan-cancer. J Clin Oncol 37(4):286–295

    Article  CAS  Google Scholar 

  11. Tanakaya K (2019) Current clinical topics of Lynch syndrome. Int J Clin Oncol 24(9):1013–1019

    Article  CAS  Google Scholar 

  12. Fang YL, Li N, Zhi XF, Zheng J, Liu Y, Pu LJ, et al. Discovery of specific mutations in spinal muscular atrophy patients by next-generation sequencing. Neurol Sci. 2020 Sep 7. doi: https://doi.org/10.1007/s10072-020-04697-8. Online ahead of print

  13. Boland PM, Yurgelun MB, Boland CR (2018 May) Recent progress in Lynch syndrome and other familial colorectal cancer syndromes. CA Cancer J Clin 68(3):217–231

    Article  Google Scholar 

  14. Bats AS, Rossi L, Le Frere-Belda MA, Narjoz C, Cournou C, Gosset M, Ngo C et al (2017 Dec) Lynch syndrome and endometrial cancer. Bull Cancer 104(12):1013–1021

    Article  Google Scholar 

  15. Chang TR, Albright KC, Boehme AK, Dorsey A, Sartor EA, Kruse-Jarres R, Leissinger C, Martin-Schild S (2014 Mar) Factor VIII in the setting of acute ischemic stroke among patients with suspected hypercoagulable state. Clin Appl Thromb Hemost 20(2):124–128

    Article  Google Scholar 

  16. Rondon AMR, Kroone C, Kapteijn MY, Versteeg HH, Buijs JT (2019 Jun) Role of tissue factor in tumor progression and cancer-associated thrombosis. Semin Thromb Hemost 45(4):396–412

    Article  CAS  Google Scholar 

  17. De Robertis R, Paiella S, Cardobi N, Landoni L, Tinazzi Martini P, Ortolani S et al (2018 Mar) Tumor thrombosis: a peculiar finding associated with pancreatic neuroendocrine neoplasms. A pictorial essay. Abdom Radiol (NY) 43(3):613–619

    Article  Google Scholar 

  18. Yokoyama T, Takehara K, Sugimoto N, Kaneko K, Fujimoto E, Okazawa-Sakai M, Okame S, Shiroyama Y, Yokoyama T, Teramoto N, Ohsumi S, Saito S, Imai K, Sugano K (2018) Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review. BMC Cancer 18(1):576

    Article  Google Scholar 

  19. Bouvet D, Bodo S, Munier A, Guillerm E, Bertrand R, Colas C, Duval A, Coulet F, Muleris M (2019 Aug) Methylation tolerance-based functional assay to assess variants of unknown significance in the MLH1 and MSH2 genes and identify patients with Lynch syndrome. Gastroenterology. 157(2):421–431

    Article  CAS  Google Scholar 

  20. Lu JY, Sheng JQ (2015) Advances in the study of Lynch syndrome in China. World J Gastroenterol 21(22):6861–6871

    Article  Google Scholar 

Download references

Funding

This research was funded by the Key Research and Development Program of Hunan Province (No. 2020SK2063), the Natural Science Foundations of Hunan Province (No. 2020JJ4134&2020JJ4893), and the National Natural Science Foundation of China (No. 81501025).

Author information

Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China

    Mengqi Zhang, Haojun Yang, Zhuohui Chen, Yishu Fan, Xinhang Hu & Weiping Liu

Authors
  1. Mengqi Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haojun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhuohui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yishu Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xinhang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weiping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The patients were treated by Dr. Liu, Dr. Chen, Dr. Fan, and Dr. Hu who were responsible for collection of data; this manuscript was written by Dr. Zhang, Dr. Yang, and Dr. Liu.

Corresponding author

Correspondence to Weiping Liu.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

This study was approved by the ethics committee of Xiangya Hospital of Central South University. Written informed consent was obtained from the patient in this study.

Code availability

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this article was revised: The original article contains an error. In the “Discussion”, the patient’s age in the case presentation part should be 34 years old, not 43 years old.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, M., Yang, H., Chen, Z. et al. Lynch syndrome-associated repeated stroke with MLH1 frame-shift mutation. Neurol Sci 42, 1631–1635 (2021). https://doi.org/10.1007/s10072-020-04987-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-020-04987-1

Keywords

Search

Navigation