Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH1. (3rd April 2015)

• Record Type: Journal Article
• Authors: Rubboli, Guido; Veggiotti, Pierangelo; Pini, Antonella; Berardinelli, Angela; Cantalupo, Gaetano; Bertini, Enrico; Tiziano, Francesco Danilo; D'Amico, Adele; Piazza, Elena; Abiusi, Emanuela; Fiori, Stefania; Pasini, Elena; Darra, Francesca; Gobbi, Giuseppe; Michelucci, Roberto
• Is Part Of: Epilepsia. Volume 56:issue 5(2015:May)
• Page Start: 692
• Page End: 698
• Publication Date: 2015-04-03
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12977
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12977-abs-0001"> <title>Summary</title> <sec id="epi12977-sec-0001" sec-type="section"> <title>Objective</title> <p>To present the clinical features and the results of laboratory investigations in three patients with spinal muscular atrophy associated with progressive myoclonic epilepsy (SMA‐PME), a rare condition caused by mutations in the <italic>N</italic>‐acylsphingosine amidohydrosilase 1 (<italic>ASAH1</italic>) gene.</p> </sec> <sec id="epi12977-sec-0002" sec-type="section"> <title>Methods</title> <p>The patients were submitted to clinical evaluation, neurophysiologic investigations (that included wakefulness and sleep electroencephalography [EEG], video‐polygraphic recording with jerk‐locked back‐averaging, multimodal evoked potentials, and electromyography), brain magnetic resonance imaging (MRI), biochemical screening, muscle and skin biopsies, and molecular genetic analysis.</p> </sec> <sec id="epi12977-sec-0003" sec-type="section"> <title>Results</title> <p>The main clinical features were onset in childhood with proximal muscular weakness, generalized epilepsy with absences and myoclonic seizures, cognitive impairment of variable degree; the course was progressive with muscle wasting and uncontrolled epileptic seizures. In one patient, earlier onset before the age of 2 years was associated with a more complex clinical picture, with abnormal eye movements, progressive cognitive impairment, and a more rapid and severe course. EEG/polygraphic data were consistent with PME, demonstrating generalized spike‐and‐wave discharges, evidence of positive and negative myoclonia, and prominent photosensitivity. In one patient, transcranial magnetic stimulation showed a hyperexcitable motor cortex, whereas somatosensory evoked potentials were unaffected. Possible involvement of the central acoustic and visual pathways was suggested by abnormal auditory and visual evoked potentials. Muscle biopsies showed typical signs of neurogenic damage. Molecular genetic analysis showed mutations of the <italic>ASAH1</italic> gene.</p> </sec> <sec id="epi12977-sec-0004" sec-type="section"> <title>Significance</title> <p>Our data indicate that SMA‐PME associated with <italic>ASAH1</italic> mutations is a genetically distinct condition with specific clinical and neurophysiologic features. Further studies are warranted to explore the role of the <italic>ASAH1</italic> gene in muscle and brain function.</p> </sec> </abstract>