Adult-onset non-5q proximal spinal muscular atrophy: a comprehensive review

Abstract

Background: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. Objective: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. Methods: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Results: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. Conclusions: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.

RESUMO

Antecedentes: Atrofia muscular espinhal (AME) de início no adulto representa um grupo de doenças neurodegenerativas hereditárias em expansão na prática clínica. Objetivo: Este artigo de revisão sintetiza os principais aspectos clínicos, genéticos, radiológicos, bioquímicos e neurofisiológicos relacionados às formas clássicas e recentemente descritas de AME proximal do adulto. Métodos: Os autores realizaram uma revisão crítica não sistemática descrevendo as principais apresentações de AME proximal de início no adulto. Resultados: Previamente restrito às apresentações de AME tipo 4 associada ao gene SMN1, este grupo atualmente envolve mais de 15 diferentes condições clínicas que compartilham entre si a presença de comprometimento progressivo e simétrico do neurônio motor inferior se iniciando no adulto ou no idoso. Novos subtipos clínicos e genéticos de AME proximal de início no adulto foram reconhecidas e são alvos atuais de estudos direcionados a aspectos neurorradiológicos, patológicos e genéticos. Conclusões: Este novo grupo complexo de doenças raras tipicamente se apresenta com doença do neurônio motor inferior em associação com outros sinais de comprometimento neurológico ou sistêmico, os quais apresentam padrões relativamente específicos para cada subtipo genético.

Keywords:

Muscular Atrophy, Spinal - Neurodegenerative Diseases - Motor Neuron Disease - Neuromuscular Diseases

Palavras-chave:

Atrofia Muscular Espinhal - Doenças Neurodegenerativas - Doença dos Neurônios Motores - Doenças Neuromusculares

Authors’ contributions:

WBVRP: conception, organization, and execution of manuscript project, writing of the first draft, and review and critique of manuscript; PVSS, EAG: conception, organization, and execution of manuscript project, writing of the first draft of manuscript; BMLB, JMVAF, RILM: conception, and organization of manuscript project, writing of the first draft of manuscript; IBF, ASBO: conception of manuscript project, writing of the first draft, review and critique of manuscript.

Publication History

Received: 05 September 2020

Accepted: 24 December 2020

Article published online:
07 June 2023

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