{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:16:48Z","timestamp":1790691408763,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,4,3]],"date-time":"2015-04-03T00:00:00Z","timestamp":1428019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To present the clinical features and the results of laboratory investigations in three patients with spinal muscular atrophy associated with progressive myoclonic epilepsy (<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content>), a rare condition caused by mutations in the <jats:italic>N<\/jats:italic>\u2010acylsphingosine amidohydrosilase 1 (<jats:italic><jats:styled-content style=\"fixed-case\">ASAH<\/jats:styled-content>1<\/jats:italic>) gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The patients were submitted to clinical evaluation, neurophysiologic investigations (that included wakefulness and sleep electroencephalography [<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>], video\u2010polygraphic recording with jerk\u2010locked back\u2010averaging, multimodal evoked potentials, and electromyography), brain magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>), biochemical screening, muscle and skin biopsies, and molecular genetic analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats: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\u00a0years was associated with a more complex clinical picture, with abnormal eye movements, progressive cognitive impairment, and a more rapid and severe course. <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\/polygraphic data were consistent with <jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content>, demonstrating generalized spike\u2010and\u2010wave 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 <jats:italic><jats:styled-content style=\"fixed-case\">ASAH<\/jats:styled-content>1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our data indicate that <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PME<\/jats:styled-content> associated with <jats:italic><jats:styled-content style=\"fixed-case\">ASAH<\/jats:styled-content>1<\/jats:italic> mutations is a genetically distinct condition with specific clinical and neurophysiologic features. Further studies are warranted to explore the role of the <jats:italic><jats:styled-content style=\"fixed-case\">ASAH<\/jats:styled-content>1<\/jats:italic> gene in muscle and brain function.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12977","type":"journal-article","created":{"date-parts":[[2015,4,3]],"date-time":"2015-04-03T15:00:27Z","timestamp":1428073227000},"page":"692-698","source":"Crossref","is-referenced-by-count":41,"title":["Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in <i><scp>ASAH<\/scp>1<\/i>"],"prefix":"10.1111","volume":"56","author":[{"given":"Guido","family":"Rubboli","sequence":"first","affiliation":[{"name":"Danish Epilepsy Center Filadelfia\/University of Copenhagen Dianalund Denmark"},{"name":"Neurology Unit Bellaria Hospital IRCCS Institute of Neurological Sciences Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierangelo","family":"Veggiotti","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences Child Neuropsychiatry Unit IRCCS C. Mondino National Neurological Institute University of Pavia Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Pini","sequence":"additional","affiliation":[{"name":"Child Neurology Unit Bellaria Hospital IRCCS Institute of Neurological Sciences Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Berardinelli","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit IRCCS C. Mondino National Neurological Institute Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Cantalupo","sequence":"additional","affiliation":[{"name":"Department of Life and Reproduction Sciences University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[{"name":"IRCCS Laboratory of Molecular Medicine Bambino Gesu' Children's Research Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Danilo","family":"Tiziano","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute Catholic University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"D'Amico","sequence":"additional","affiliation":[{"name":"IRCCS Laboratory of Molecular Medicine Bambino Gesu' Children's Research Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Piazza","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit IRCCS C. Mondino National Neurological Institute Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Abiusi","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute Catholic University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Fiori","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute Catholic University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pasini","sequence":"additional","affiliation":[{"name":"Neurology Unit Bellaria Hospital IRCCS Institute of Neurological Sciences Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Darra","sequence":"additional","affiliation":[{"name":"Department of Life and Reproduction Sciences University of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Child Neurology Unit Bellaria Hospital IRCCS Institute of Neurological Sciences Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Michelucci","sequence":"additional","affiliation":[{"name":"Neurology Unit Bellaria Hospital IRCCS Institute of Neurological Sciences Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410060309"},{"key":"e_1_2_6_3_1","first-page":"141","article-title":"Progressive myoclonic epilepsy","volume":"20","author":"Lance WJ","year":"1984","journal-title":"Clin Exp Neurol"},{"key":"e_1_2_6_4_1","first-page":"313","article-title":"Unusual familial association of epilepsy, myoclonus and muscular atrophy. 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