Dados do Trabalho

Título

Spinal muscular atrophy with predominant lower extremity type I (SMALED1) with no signs other than pure motor symptoms

RESUMO

Presentation of the case: 5-year-old boy , with a history of delayed motor development. It evolved with proximal weakness in the lower limbs (Gowers signal positive), hyperreflexia, atrophy in the legs and lordosis. Electroneuromyography showed chronic signs of denervation with normal sensory conduction. The father, not genetically tested, has atrophy in his legs. A large DNA panel of neuromuscular diseases (NGS) detected the heterozygous pathogenic variant, chr14:101.986.017 C>T (or alternatively c.1792C>T - ENST00000360184) in the DYNC1H1 gene. Considering the clinical and electrophysiological data and the pathogenic variant, this is a case of SMALED1 due to a pathogenic variant of the DYNC1H1 gene. Discussion: Spinal Muscular Atrophies (SMA) correspond to a group of hereditary diseases caused by loss or abnormal development of lower motor neurons. The major cause is SMA associated with homozygous deletion of exons 7 and 8 of the SMN1 gene on chromosome 5q. Other causes, called non-5q SMA, are less frequent and poorly recognized. One of these is SMALED1 (Spinal muscular atrophy lower extremity predominant; OMIM #158600), of autosomal dominant inheritance, associated with the DYNC1H1 gene (OMIM #600112), with a less aggressive evolution than 5q SMA. This gene lead to two human motor neuropathies, SMALED and axonal Charcot-Marie-Tooth (CMT) disease. Final comments: the phenotype SMALED1 show childhood onset, lower limb weakness, associated with arthrogryposis and cognitive impairment. There is great clinical variability, with cases of adult onset (after 18 years) and purely motor and proximal cases, simulating a myopathy, as in the case described.

Palavras Chave

Non-5q Spinal Muscular Atrophy, SMALED1, DYNC1H1

Área

Doenças Neuromusculares