Clinical and genetic heterogeneity in hereditary spastic paraplegias: From SPG1 to SPG72 and still counting
Revue Neurologique. 2015-06-01; 171(6-7): 505-530
DOI: 10.1016/J.NEUROL.2015.02.017
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1. Rev Neurol (Paris). 2015 Jun-Jul;171(6-7):505-30. doi:
10.1016/j.neurol.2015.02.017. Epub 2015 May 23.
Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1
to SPG72 and still counting.
Klebe S(1), Stevanin G(2), Depienne C(3).
Author information:
(1)Department of neurology, university hospital Würzburg, Josef-Schneider-Straße
11, 97080 Würzburg, Germany.
(2)Sorbonne universités, UPMC université Paris 06, 91-105, boulevard de
l’Hôpital, 75013 Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, 47/83,
boulevard de l’Hôpital, 75013 Paris, France; École pratique des hautes études,
4-14, rue Ferrus, 75014 Paris, France; Département de génétique, AP-HP, hôpital
Pitié-Salpêtrière, 47/83, boulevard de l’Hôpital, 75013 Paris, France.
(3)Sorbonne universités, UPMC université Paris 06, 91-105, boulevard de
l’Hôpital, 75013 Paris, France; ICM, CNRS UMR 7225, Inserm U 1127, 47/83,
boulevard de l’Hôpital, 75013 Paris, France; Département de génétique, AP-HP,
hôpital Pitié-Salpêtrière, 47/83, boulevard de l’Hôpital, 75013 Paris, France.
Electronic address: .
Hereditary spastic paraplegias (HSPs) are genetically determined
neurodegenerative disorders characterized by progressive weakness and spasticity
of lower limbs, and are among the most clinically and genetically heterogeneous
human diseases. All modes of inheritance have been described, and the recent
technological revolution in molecular genetics has led to the identification of
76 different spastic gait disease-loci with 59 corresponding spastic paraplegia
genes. Autosomal recessive HSP are usually associated with diverse additional
features (referred to as complicated forms), contrary to autosomal dominant HSP,
which are mostly pure. However, the identification of additional mutations and
families has considerably enlarged the clinical spectra, and has revealed a huge
clinical variability for almost all HSP; complicated forms have also been
described for primary pure HSP subtypes, adding further complexity to the
genotype-phenotype correlations. In addition, the introduction of next generation
sequencing in clinical practice has revealed a genetic and phenotypic overlap
with other neurodegenerative disorders (amyotrophic lateral sclerosis,
neuropathies, cerebellar ataxias, etc.) and neurodevelopmental disorders,
including intellectual disability. This review aims to describe the most recent
advances in the field and to provide genotype-phenotype correlations that could
help clinical diagnoses of this heterogeneous group of disorders.
Copyright © 2015 Elsevier Masson SAS. All rights reserved.
DOI: 10.1016/j.neurol.2015.02.017
PMID: 26008818 [Indexed for MEDLINE]