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Open Access 01-11-2018 | Original Article

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant

Authors: Mayada Helal, Neda Mazaheri, Bita Shalbafan, Reza Azizi Malamiri, Nafi Dilaver, Rebecca Buchert, Javad Mohammadiasl, Neda Golchin, Alireza Sedaghat, Mohammad Yahya Vahidi Mehrjardi, Tobias B. Haack, Olaf Riess, Wendy K. Chung, Hamid Galehdari, Gholamreza Shariati, Reza Maroofian

Published in: Neurological Sciences | Issue 11/2018

Abstract

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2–48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course.

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Title: Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant
Authors: Mayada Helal
Neda Mazaheri
Bita Shalbafan
Reza Azizi Malamiri
Nafi Dilaver
Rebecca Buchert
Javad Mohammadiasl
Neda Golchin
Alireza Sedaghat
Mohammad Yahya Vahidi Mehrjardi
Tobias B. Haack
Olaf Riess
Wendy K. Chung
Hamid Galehdari
Gholamreza Shariati
Reza Maroofian
Publication date: 01-11-2018
Publisher: Springer Milan
Published in: Neurological Sciences / Issue 11/2018
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-018-3526-8

At a glance: The STEP trials

Springer Medicine

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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