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European Journal of Pediatrics

, Volume 175, Issue 1, pp 137–141 | Cite as

Sporadic paraganglioma caused by de novo SDHB mutations in a 6-year-old girl

  • Hideaki Imamura
  • Koji Muroya
  • Etsuko Tanaka
  • Takao Konomoto
  • Hiroshi Moritake
  • Takeshi Sato
  • Noriko Kimura
  • Kazuhiro Takekoshi
  • Hiroyuki Nunoi
Short Communication

Abstract

Germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene (SDHB) cause susceptibility to paragangliomas and pheochromocytomas; however, it is exceedingly rare in childhood and especially in sporadic cases. We report the first Japanese pediatric case of paraganglioma with a de novo mutation in the SDHB gene. A 6-year-old girl with convulsions and hypertension was found to have a paravertebral abdominal tumor. Urinary and blood examinations revealed markedly elevated levels of norepinephrine. Following treatment for hypertension, the tumor was removed completely and histological findings were consistent with paraganglioma. Immunohistochemistry studies demonstrated the absence of SDHB protein expression, indicating an underlying SDH mutation with high probability. Germline mutation analysis of the SDHB gene revealed a heterozygous splice site mutation in intron 4 (C.423 + 1G > A). Subsequently, a second somatic genetic change was confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis, showing that deletion of the wild-type allele resulted in loss of function of SDHB. No germline mutations in SDHB were detected in her parents.

Conclusion: Genetic testing should be considered for pediatric patients with paragangliomas, even in the absence of familial history, as closer lifelong screening to detect the development of malignancy will be required for patients with SDHB mutations.

What is Known

Most sporadic cases of paraganglioma with SDHB mutations occur between adolescence and adulthood.

Screening methods for carriers of SDHB mutations assessing recurrence and detecting developing metastases are yet to be standardized.

What is New

The current case of an extra-adrenal paraganglioma with a de novo SDHB mutation had an onset at 6 years.

We suggest much closer periodical observation for these high-risk children.

Keywords

Paraganglioma Childhood Succinate dehydrogenase complex subunit B Screening Multiplex ligation-dependent probe amplification Loss of heterozygosity 

Abbreviations

LOH

Loss of heterozygosity

MLPA

Multiplex ligation-dependent probe amplification

PCC

Pheochromocytoma

PGL

Paraganglioma

SDH

Succinate dehydrogenase

SDHB

Succinate dehydrogenase complex subunit B

Notes

Acknowledgments

We are grateful to Hirohito Shima and Keiko Matsubara, Department of Molecular Endocrinology, National Research Institute for Child Health and Development, for performing microsatellite analysis to confirm the paternity.

Funding

None declared.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethics committee of the Medical Faculty of Miyazaki University, Miyazaki, Japan, and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Authors’ contribution

HI, ET, and TK clinically managed the patient. HI wrote the manuscript under HN’s supervision. KM and TS were responsible for the genetic analysis. NK was responsible for the immunohistochemistry study of SDHB and wrote the manuscript. KT and HM contributed to genetic analysis and interpretation. KM, TS, NK, KT, HM, and HN critically reviewed the manuscript. All the authors approved the final copy of the manuscript.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Hideaki Imamura
    • 1
  • Koji Muroya
    • 2
  • Etsuko Tanaka
    • 1
  • Takao Konomoto
    • 1
  • Hiroshi Moritake
    • 1
  • Takeshi Sato
    • 3
  • Noriko Kimura
    • 4
  • Kazuhiro Takekoshi
    • 5
  • Hiroyuki Nunoi
    • 1
  1. 1.Division of Pediatrics, Department of Reproductive and Developmental Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
  2. 2.Department of Endocrinology and MetabolismKanagawa Children’s Medical CenterYokohamaJapan
  3. 3.Department of PediatricsKeio University School of MedicineShinjuku-kuJapan
  4. 4.Department of Clinical Research, Pathology Division, National Hospital OrganizationHakodate HospitalHakodateJapan
  5. 5.Division of Sports Science, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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