A new study by an international research team characterized three new cases of a rare medical condition where spinal muscular atrophy (SMA) is associated with progressive myoclonic epilepsy (PME). The study is entitled “Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH1” and was recently published in the journal Epilepsia.
SMA is a rare, devastating motor neuron disease and one of the leading genetic causes of pediatric mortality, occurring in approximately 1 in every 6,000 to 10,000 newborns. It is characterized by the degeneration of nerves controlling muscles and voluntary movement, resulting in muscle weakness, atrophy, paralysis and eventually death. SMA is the result of a mutation or deletion in a gene called survival of motor neuron 1 (SMN1), which causes insufficient production of the SMN protein.
SMA has been previously associated with another condition called PME, a group of rare syndromes involving the central nervous system and characterized by muscle contractions (myoclonus) and seizures (epilepsy) that leads to unsteadiness, muscle rigidity and neurological deterioration. The genetic cause underlying this SMA-PME rare condition was proposed to be a mutation in the gene N-acylsphingosine amidohydrosilase 1 (ASAH1). In this study, researchers assessed three new SMA-PME patients in order to better understand the phenotype linked to this condition.
The research team analyzed the three patients (all girls aged 3, 8 and 18 years old) in terms of clinical and neurophysiological parameters, including brain magnetic resonance imaging (MRI), electromyography (EMG), and wakefulness and sleep electroencephalography (EEG). Skin and muscle biopsies, as well as molecular genetic analysis were also performed.
Researchers found that the main clinical features of SMA-PME condition were onset during childhood characterized by proximal muscular weakness, and later appearance of cognitive impairment of variable degree, and generalized epilepsy with absences and myoclonic seizures. The course of the disease was found to be progressive and associated to uncontrolled epileptic seizures and muscle wasting. Mutations in the ASAH1 gene were found in the three patients and the muscle biopsies revealed typical signs of neurogenic damage.
Taken together with previous case reports, the team reported that patients with a childhood SMA-PME onset usually experience a more rapid and severe disease course, whereas patients with juvenile/adult onset have a slower disease evolution, without cognitive impairment and being responsive to antiepileptic drugs.
The research team concluded that the SMA-PME condition linked to ASAH1 mutations has distinct genetic, clinical and neurophysiologic features. The team suggests that further studies should explore the role of ASAH1 in brain and muscle function.