A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings

Alexandros A. Polymeris, Alessandra Tessa, Katherine Anagnostopoulou, Anna Rubegni, Daniele Galatolo, Argirios Dinopoulos, Artemis D. Gika, Sotiris Youroukos, Eleni Skouteli, Filippo M. Santorelli, Roser Pons

Research output: Contribution to journalArticle

Abstract

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. Adult case series dominate the literature, and there have been only a few studies in children. The purpose of this study is to describe our experience with pediatric HSP in Greece. We report the clinical and genetic findings in our patients and aim to offer insights into the diagnostic difficulties of childhood-onset disease. A series of 15 Greek children affected by pure HSP underwent extensive diagnostic investigations. Molecular analysis included whole exome sequencing (WES) or consecutive screening of candidate genes ATL1, SPAST, REEP1, and CYP7B1. WES performed in three cases yielded previously reported mutations in ATL1 and CYP7B1, and a variant c.397C>T of unknown significance in SPG7. Candidate gene screening performed in the remaining patients identified previously reported mutations in ATL1 (2), SPAST (2), and REEP1 (1), and two novel mutations, c.1636G>A and c.1413+3_6delAAGT, in SPAST. In six cases, the mutations were inherited from their parents, while in three cases, the mutations were apparently de novo. Our data confirm the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. De novo occurrence of HSP does not seem to be uncommon. Candidate gene studies guided by diagnostic algorithms and WES seem both to be reasonable genetic testing strategies.

Original languageEnglish
Pages (from-to)1604-1611
Number of pages8
JournalJournal of Neurology
Volume263
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

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Keywords

  • Children
  • Early onset
  • Hereditary spastic paraplegia
  • Mutation screening
  • Pure

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Polymeris, A. A., Tessa, A., Anagnostopoulou, K., Rubegni, A., Galatolo, D., Dinopoulos, A., Gika, A. D., Youroukos, S., Skouteli, E., Santorelli, F. M., & Pons, R. (2016). A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings. Journal of Neurology, 263(8), 1604-1611. https://doi.org/10.1007/s00415-016-8179-z