Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance re...

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Autores principales:	Liena E. O. Elsayed, Isra Zuhair Eltazi, Ammar E. Ahmed, Giovanni Stevanin
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	spastic paraplegia clinical spectrum genetic heterogeneity phenotype-genotype correlation molecular mechanisms diagnostic yield Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a589d04b400a478fa0e38fbd7132dd6c
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spelling	oai:doaj.org-article:a589d04b400a478fa0e38fbd7132dd6c2021-12-01T07:30:52ZInsights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview2296-889X10.3389/fmolb.2021.690899https://doaj.org/article/a589d04b400a478fa0e38fbd7132dd6c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.690899/fullhttps://doaj.org/toc/2296-889XHereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.Liena E. O. ElsayedLiena E. O. ElsayedIsra Zuhair EltaziAmmar E. AhmedGiovanni StevaninGiovanni StevaninGiovanni StevaninFrontiers Media S.A.articlespastic paraplegiaclinical spectrumgenetic heterogeneityphenotype-genotype correlationmolecular mechanismsdiagnostic yieldBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spastic paraplegia clinical spectrum genetic heterogeneity phenotype-genotype correlation molecular mechanisms diagnostic yield Biology (General) QH301-705.5
spellingShingle	spastic paraplegia clinical spectrum genetic heterogeneity phenotype-genotype correlation molecular mechanisms diagnostic yield Biology (General) QH301-705.5 Liena E. O. Elsayed Liena E. O. Elsayed Isra Zuhair Eltazi Ammar E. Ahmed Giovanni Stevanin Giovanni Stevanin Giovanni Stevanin Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
description	Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders that have the core clinical presentation of pyramidal syndrome which starts typically in the lower limbs. They can present as pure or complex forms with all classical modes of monogenic inheritance reported. To date, there are more than 100 loci/88 spastic paraplegia genes (SPG) involved in the pathogenesis of HSP. New patterns of inheritance are being increasingly identified in this era of huge advances in genetic and functional studies. A wide range of clinical symptoms and signs are now reported to complicate HSP with increasing overall complexity of the clinical presentations considered as HSP. This is especially true with the emergence of multiple HSP phenotypes that are situated in the borderline zone with other neurogenetic disorders. The genetic diagnostic approaches and the utilized techniques leave a diagnostic gap of 25% in the best studies. In this review, we summarize the known types of HSP with special focus on those in which spasticity is the principal clinical phenotype (“SPGn” designation). We discuss their modes of inheritance, clinical phenotypes, underlying genetics, and molecular pathways, providing some observations about therapeutic opportunities gained from animal models and functional studies. This review may pave the way for more analytic approaches that take into consideration the overall picture of HSP. It will shed light on subtle associations that can explain the occurrence of the disease and allow a better understanding of its observed variations. This should help in the identification of future biomarkers, predictors of disease onset and progression, and treatments for both better functional outcomes and quality of life.
format	article
author	Liena E. O. Elsayed Liena E. O. Elsayed Isra Zuhair Eltazi Ammar E. Ahmed Giovanni Stevanin Giovanni Stevanin Giovanni Stevanin
author_facet	Liena E. O. Elsayed Liena E. O. Elsayed Isra Zuhair Eltazi Ammar E. Ahmed Giovanni Stevanin Giovanni Stevanin Giovanni Stevanin
author_sort	Liena E. O. Elsayed
title	Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
title_short	Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
title_full	Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
title_fullStr	Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
title_full_unstemmed	Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview
title_sort	insights into clinical, genetic, and pathological aspects of hereditary spastic paraplegias: a comprehensive overview
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/a589d04b400a478fa0e38fbd7132dd6c
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Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

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