Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.

Mutations in Nav1.4 and Nav1.5 α-subunits have been associated with muscular and cardiac channelopathies, respectively.

A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.

Objective: To determine the molecular basis of a complex phenotype of congenital muscle weakness observed in an isolated but consanguineous patient.

Methods: The proband was evaluated clinically and neurophysiologically over a period of 15 years. Genetic testing of candidate genes was performed.

Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations.

Objective: Neonatal diabetes secondary to mutations in potassium-channel subunits is a rare disease but constitutes a paradigm for personalized genetics-based medicine, as replacing the historical treatment with insulin injections with oral sulfonylurea (SU) therapy has been proven beneficial. SU receptors are widely expressed in the brain, and we therefore evaluated potential effects of SU on neurodevelopmental parameters, which are known to be unresponsive to insulin.

Research Design And Methods: We conducted a prospective single-center study.

Focal and abnormally persistent paralysis associated with congenital paramyotonia.

Mutations of the skeletal muscle voltage-gated sodium channel (NaV1.4) are an established cause of several clinically distinct forms of periodic paralysis and myotonia. Focal paresis has sometimes already been described.

Episodic weakness due to mitochondrial DNA MT-ATP6/8 mutations.

Objective: To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide.

Methods: Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts.

Results: Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations.

EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders.

Objectives: These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated.

Search Strategy: To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed.

Results: The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy.

Homozygosity for dominant mutations increases severity of muscle channelopathies.

Muscle channelopathies caused by mutations in the SCN4A gene that encodes the muscle sodium channel are transmitted by autosomal-dominant inheritance. We report herein the first cases of homozygous patients for sodium channel mutations responsible for paramyotonia congenita (I1393T) or hypokalemic periodic paralysis (R1132Q). A parallel was drawn between this unprecedented situation and that of myotonia congenita by including patients homozygous or heterozygous for the CLCN1 I556N channel mutation, which is known for incomplete dominance and penetrance.

[Periodic paralysis: new pathophysiological aspects].

Periodic paralyses are neuromuscular disorders characterized by attacks of muscle weakness coinciding with changes in blood potassium levels. They are thus classified as hypokalaemic, normokalaemic or hyperkalaemic. Most forms are genetic, with autosomal dominant inheritance.

Glucocorticoids may trigger attacks in several types of periodic paralysis.

Hypokalemic periodic paralysis is a rare disorder characterized by episodic attacks of muscle flaccidity associated with low serum potassium levels. We report twelve patients with normokalemic and hypokalemic periodic paralysis due to various mutations who developed hypokalemic paralytic episodes following a single dose or short-term administration of glucocorticoids. We hypothesize that glucocorticoids cause hypokalemia due to their stimulation of the Na(+)-K(+) ATPase mediated by insulin and amylin and due to their side effect of insulin resistance resulting in hyperglycemia.

Periodic paralysis.

Periodic paralyses are rare diseases characterized by severe episodes of muscle weakness concomitant to variations in blood potassium levels. It is thus usual to differentiate hypokalemic, normokalemic, and hyperkalemic periodic paralysis. Except for thyrotoxic hypokalemic periodic paralysis and periodic paralyses secondary to permanent changes of blood potassium levels, all of these diseases are of genetic origin, transmitted with an autosomal-dominant mode of inheritance.