SHH medulloblastoma in a young adult with a TCF4 germline pathogenic variation
- 249 Downloads
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) . 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).
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.
- 1.Amiel J, Rio M, de Pontual L, Redon R, Malan V, Boddaert N et al (2007) Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am J Hum Genet 80:988–993. https://doi.org/10.1086/515582 CrossRefGoogle Scholar
- 4.Inoue K, Fry EA (2017) Haploinsufficient tumor suppressor genes. Adv Med Biol 118:83–122Google Scholar
- 10.Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C, Groebner S et al (2018) Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol 19:785–798. https://doi.org/10.1016/S1470-2045(18)30242-0 CrossRefGoogle Scholar