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Acta Neuropathologica

, Volume 137, Issue 4, pp 675–678 | Cite as

SHH medulloblastoma in a young adult with a TCF4 germline pathogenic variation

  • Maud Blanluet
  • Julien Masliah-Planchon
  • Irina Giurgea
  • Franck Bielle
  • Elodie Girard
  • Mamy Andrianteranagna
  • Stéphane Clemenceau
  • Christine Bourneix
  • Lydie Burglen
  • Diane Doummar
  • Audrey Rapinat
  • Badreddine Mohand Oumoussa
  • Olivier Ayrault
  • Celio Pouponnot
  • David Gentien
  • Gaëlle Pierron
  • Olivier Delattre
  • François Doz
  • Franck BourdeautEmail author
Correspondence

Pitt–Hopkins syndrome (PTHS, MIM #610954) is a rare neurodevelopmental disease due to heterozygous loss of function variants in the TCF4 gene (transcription factor 4, MIM #602272) [1]. TCF4 encodes a basic helix-loop-helix (bHLH) transcription factor which is highly expressed in the nervous system during early development and is involved in cellular proliferation and differentiation. To date, approximately 200 PTHS patients have been reported since the first clinical description in 1978 [1, 11, 12]. The limited number of cases described and their early age precludes establishing a comprehensive phenotype, especially regarding cancer predisposition. Here we report the case of a 27-year-old woman affected by PTHS who developed a medulloblastoma (MB).

The PTHS patient, previously reported (P12) [ 11], harbored a typical facial gestalt, hypotonia, hyperventilation, had delayed walking, and never acquired language. The PTHS diagnosis was confirmed by identification of the heterozygous de...

Notes

Acknowledgements

We thank Joshua Waterfall for his help in writing the manuscript.

Compliance with ethical standards

Conflict of interest

The author(s) declare that they have no conflict of interest.

Supplementary material

401_2019_1983_MOESM1_ESM.pptx (625 kb)
Supplementary Figure 1. Histopathological features of the tumor. (a) Hematoxylin and eosin staining showed a histological aspect of classic medulloblastoma with necrosis. (b) Immunostaining showed a diffusely high Ki67 proliferation index, (c) a maintained expression of SMARCB1/INI1, and (d) a mild positivity of P53. (e) Reticulin staining showed no reticulinic network between tumor cells. (f) Immunostaining showed a membrane staining for Beta-catenin, and (g) a strong positivity for Filamin-1 and (h) GAB1 favoring the genetic group of SHH-activated medulloblastomas (PPTX 624 kb)
401_2019_1983_MOESM2_ESM.pptx (122 kb)
Supplementary Figure 2. Methylation and genomic tumor data. (a) t-distributed Stochastic Neighbor Embedding (t-SNE) analysis using DNA methylation data (generated using HumanMethylation450K array type) of glioblastoma (GBM) and medulloblastoma (MB) samples published in Capper et al. (2018) [2] and DNA methylation data of our case (generated using HumanMethylationEPIC array type) named MB699. (b) MNP2.0-based DNA methylation class prediction calibrated scores for our case (DKFZ classifier version: 11b4). The other scores (data not shown) are inferior to 0.01. (c) Analysis of tumor DNA of our case by the Curie Institute custom cancer panel assessing known cancer-related genes (8 alterations), compared with the proportion of relevant tumor DNA alterations of these genes for all SHH MB (SHH MB column) and TCF4 mutated SHH MB (TCF4 mutated SHH MB column), from Northcott et al. (2017) [6] (PPTX 122 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Maud Blanluet
    • 1
  • Julien Masliah-Planchon
    • 1
    • 2
  • Irina Giurgea
    • 3
    • 4
  • Franck Bielle
    • 5
  • Elodie Girard
    • 6
  • Mamy Andrianteranagna
    • 2
  • Stéphane Clemenceau
    • 7
  • Christine Bourneix
    • 1
  • Lydie Burglen
    • 8
  • Diane Doummar
    • 9
  • Audrey Rapinat
    • 10
  • Badreddine Mohand Oumoussa
    • 11
  • Olivier Ayrault
    • 12
    • 13
  • Celio Pouponnot
    • 12
    • 13
  • David Gentien
    • 10
  • Gaëlle Pierron
    • 1
    • 2
  • Olivier Delattre
    • 1
    • 2
    • 14
  • François Doz
    • 2
    • 15
  • Franck Bourdeaut
    • 2
    • 14
    Email author
  1. 1.Unité de Génétique SomatiqueInstitut CurieParisFrance
  2. 2.Pediatric Oncology Department, SIREDO Oncology Centre (Care, Innovation, Research in Pediatric, Adolescent and Young Adults Oncology), Institut CurieParis Cedex 05France
  3. 3.UF de Génétique Moléculaire, Hôpital Armand Trousseau, APHPParisFrance
  4. 4.Sorbonne Université, INSERM, UMR S933ParisFrance
  5. 5.Departement de Neuropathologie, Groupe Hospitalier Pitié-SalpêtrièreAP-HPParisFrance
  6. 6.INSERM U900, Institut CurieParisFrance
  7. 7.Neurochirurgie, GH Pitie-Salpêtrière-Charles Foix, APHPParisFrance
  8. 8.Centre de Référence Maladies Rares “Malformations et Maladies Congénitales du Cervelet”et Département de Génétique, Hôpital Armand Trousseau, GHUEP, APHPParisFrance
  9. 9.Département de Neuropédiatrie, Hôpital Armand Trousseau, APHPParisFrance
  10. 10.Translational Research Department, Genomics Platform, Institut CuriePSL Research UniversityParisFrance
  11. 11.Sorbonne Université, InsermUMS Omique, Plateforme Post-Génomique de la Pitié-Salpêtrière, P3SParisFrance
  12. 12.Université Paris Sud, Université Paris-SaclayCNRS, UMR 3347, INSERM U1021OrsayFrance
  13. 13.Institut Curie, PSL Research University, CNRS UMR, INSERMOrsayFrance
  14. 14.Inserm U830, PSL Université, Institut CurieParisFrance
  15. 15.Université Paris Descartes, Sorbonne Paris CitéParisFrance

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