Early onset hereditary neuronopathies: an update on non-5q motor neuron diseases.
Brain
; 146(3): 806-822, 2023 03 01.
Article
em En
| MEDLINE
| ID: mdl-36445400
ABSTRACT
Hereditary motor neuropathies (HMN) were first defined as a group of neuromuscular disorders characterized by lower motor neuron dysfunction, slowly progressive length-dependent distal muscle weakness and atrophy, without sensory involvement. Their cumulative estimated prevalence is 2.14/100 000 and, to date, around 30 causative genes have been identified with autosomal dominant, recessive,and X-linked inheritance. Despite the advances of next generation sequencing, more than 60% of patients with HMN remain genetically uncharacterized. Of note, we are increasingly aware of the broad range of phenotypes caused by pathogenic variants in the same gene and of the considerable clinical and genetic overlap between HMN and other conditions, such as Charcot-Marie-Tooth type 2 (axonal), spinal muscular atrophy with lower extremities predominance, neurogenic arthrogryposis multiplex congenita and juvenile amyotrophic lateral sclerosis. Considering that most HMN present during childhood, in this review we primarily aim to summarize key clinical features of paediatric forms, including recent data on novel phenotypes, to help guide differential diagnosis and genetic testing. Second, we describe newly identified causative genes and molecular mechanisms, and discuss how the discovery of these is changing the paradigm through which we approach this group of conditions.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Atrofia Muscular Espinal
/
Doença de Charcot-Marie-Tooth
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article