Association of type IV spinal muscular atrophy (SMA) with myoclonic epilepsy within a single family

Abstract

BackgroundSpinal muscular atrophies (SMAs) are a group of disorders characterized by degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. It is transmitted by autosomal recessive inheritance and most of these conditions are linked to SMN gene. Even if the clinical picture is mainly dominated by the diffuse muscular atrophy, some patients can also show atypical clinical features such as myoclonic epilepsy (“SMA plus”), which may be related to other genes. In particular, the association of SMA and progressive myoclonic epilepsy (PME) has been previously described.Case presentationWe present a case of two brothers with late onset SMA associated with a unique form of non progressive myoclonic epilepsy without cognitive impairment or ataxia. They had identical clinical and electrophysiological features.ConclusionsThe association of SMA with myoclonic epilepsy may constitute a separate and genetically independent syndrome with unique clinical and electrophysiological findings. Collection of similar cases with genetic studies is needed to define the phenotype clearly and to identify new genes and molecular pathogenetic mechanisms involved in this condition.

<p>A novel case report of spinal muscular atrophy with progressive myoclonic epilepsy from Iran</p>

“…Haliloglu et al in 2002 reported another four cases of SMA-PME in two families, with myoclonic epilepsy, progressive weakness, and tremor in common 10. More recent similar Asian cases were reported by Liyanage 2 . Also, Rubboli in Italy reported the clinical manifestations of three SMA-PME patients 11.…”

“…Spinal muscular atrophy (SMA) is a heterogeneous disease characterized by degeneration of the lower motor neurons and is usually linked to mutations of SMN-1 gene 1. The condition often presents by decreased motor function and muscle atrophy due to degeneration of anterior horn cell in the spinal cord and motor cells of lower cranial nerves nuclei 2. SMA with progressive myoclonic epilepsy (PME; OMIM #159950) is a very rare autosomal-recessive (AR) condition, that is not the result of mutation in SMN-1 gene, but is caused by mutation in the N-acylsphingosine amidohydrolase-1 (ASAH-1) gene, which is responsible for lysosomal acid-ceramidase production.…”

“…The catabolism of ceramides occurs through the activity of ceramidase; this enzyme has three different subtypes including alkaline-, neutral- and acid-ceramidase 4. Deficient activity of the latter one occurs in two rare inherited disorders: Farber disease and SMA-PME 2. SMA-PME has been characterized by a progressive muscle weakness from ages 3–7 years, plus to epilepsy, an intractable seizure, and sometimes tremor 3,5.…”