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Spinal muscular atrophy associated with progressive myoclonic epilepsy: A rare condition caused by mutations in ASAH 1
Author(s) -
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
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12977
Subject(s) - progressive myoclonus epilepsy , spinal muscular atrophy , epilepsy , medicine , myoclonic epilepsy , atrophy , clinical neurology , neuroscience , pathology , psychology , disease , psychiatry
Summary Objective 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 N ‐acylsphingosine amidohydrosilase 1 ( ASAH 1 ) gene. Methods 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. Results 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 ASAH 1 gene. Significance Our data indicate that SMA ‐ PME associated with ASAH 1 mutations is a genetically distinct condition with specific clinical and neurophysiologic features. Further studies are warranted to explore the role of the ASAH 1 gene in muscle and brain function.