Neuromuscular disorders : NMD
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Neuromuscul. Disord. · Jan 2014
Case ReportsClinical, electrophysiological and magnetic resonance findings in a family with hereditary neuropathy with liability to pressure palsies caused by a novel PMP22 mutation.
Hereditary neuropathy with liability to pressure palsies (HNPP) is a disorder mainly caused by a 1.5-Mb deletion at 17p11.2-12 (and in some rare cases by point mutations) and clinically associated with recurrent painless palsies. Here, we performed electrophysiological (motor, sensory and terminal latency index), MRI and genetic studies in a family referred for ulnar neuropathy with pain. Surprisingly, we found typical neurophysiological features of HNPP (prolongation of distal motor latencies and diffuse SNCV slowing with significant slowing of motor nerve conduction velocities). ⋯ Molecular studies identified a novel frameshift mutation in PMP22 confirming the diagnosis of HNPP. Our data suggest that neurophysiological studies are essential to characterize underdiagnosed HNPP patients referred for peripheral neuropathy. Our experience shows that MRI could be a complementary tool for the diagnosis of these patients.
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Neuromuscul. Disord. · Jan 2014
Randomized Controlled TrialPharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial.
Duchenne muscular dystrophy (DMD) is a progressive, lethal neuromuscular disorder caused by the absence of dystrophin protein due to mutations of the dystrophin gene. Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. This study assessed safety, tolerability, and pharmacokinetics of drisapersen after a single subcutaneous administration in non-ambulatory subjects. ⋯ Less than proportional increase in exposure was demonstrated over the 3-9mg/kg dose range, though post hoc analysis showed dose proportionality was more feasible over the 3-6mg/kg range. Single doses of drisapersen at 3 and 6mg/kg did not result in significant safety or tolerability concerns; however, at the 9mg/kg dose, pyrexia and transient elevations in inflammatory parameters were seen. The maximum tolerated dose of 6mg/kg drisapersen was identified for further characterization in multiple dose studies in the non-ambulant DMD population.
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Neuromuscul. Disord. · Jan 2014
Case ReportsSalbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK.
Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous disorders characterized by a neuromuscular transmission defect. In recent years, causative mutations have been identified in atleast 15 genes encoding proteins of the neuromuscular junction. Mutations in MUSK are known as a very rare genetic cause of CMS and have been described in only three families, world-wide. ⋯ Clinical symptoms included fatigable limb weakness from early childhood on. Upon diagnosis of a MUSK-related CMS at the age of 16 and 13years, respectively, treatment with salbutamol was initiated leading to an impressive improvement of clinical symptoms, while treatment with esterase inhibitors did not show any benefit. Our findings highlight the importance of a molecular diagnosis in CMS and demonstrate considerable similarities between patients with MUSK and DOK7-related CMS in terms of clinical phenotype and treatment options.