Non-dystrophic myotonias panel [10 genes]
Myotonia refers to a neurological symptom that describes the difficulty for muscle relaxation after contraction. An involvement pattern may exist, although it can also affect all muscle groups.
Among the inherited causes, two fundamental groups exist:
- Myotonic dystrophy (or myotonic muscular dystrophy, whose main form is also known as DM1, or Steinert disease): its prevalence is estimated to be 1 in 8,000 individuals. Clinically it is a multisystem disease, where myotonia is accompanied by muscle weakness, cardiac conduction problems, cataracts, and endocrine and gastrointestinal problems. The molecular mechanism consists of a trinucleotide expansion in the DMOK gene, which is why its diagnosis requires a specific test. Also, a second form of myotonic dystrophy with later onset and a typically milder course exists, called proximal myotonic myopathy (DM2, or PROMM), associated with a CCTG repeat expansion in the CNBP gene.
- Non-dystrophic myotonias belong to the channelopathy group, and their genetic defects lead to the appearance of symptoms that include myotonia, feebleness, myalgia, paralysis episodes, etc.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- CLCN1: Congenital myotonia (Thomsen/Becker)
- SCN4A: Congenital myotonia
- SCN4A: Congenital paramyotonia
- SCN4A: Hypo/hyperkalemic periodic paralysis
- CACNA1S: Hypokalemic periodic paralysis
- ATP2A1: Brody myopathy
- KCNJ2, KCNJ18, KCNJ5: Andersen-Tawil syndrome
- KCNJ18: Thyrotoxic periodic paralysis
- HSPG2: Schwartz-Jampel syndrome
- Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol 2012; 11:891-905.
- Miller TM. Differential diagnosis of myotonic disorders. Muscle Nerve 2008; 37:293-9.