Description
Skeletal Muscle Channelopathies eligibility statement:

Skeletal Muscle Channelopathies inclusion criteria (29575)
- Episodic flaccid paralysis or weakness and/or myotonia
- May develop progressive, usually proximal, weakness
- Electrophysiology including long and short exercise testing
- Intra-attack potassium documented whenever possible
- Normal renal function and thyroid function

Skeletal Muscle Channelopathies exclusion criteria (29575)
- Primary renal or endocrine problem that may be causative
- Associated loss of consciousness with attacks

Prior genetic testing guidance (29575)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Skeletal Muscle Channelopathies prior genetic testing genes (29575)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
 - Myotonia: DMPK, CNBP, SCN4A, CLCN1 (including MLPA)
 - Episodic weakness: CACNA1S, SCN4A, KCNJ2

Closing statement (29575)
These requirements will be kept under continual review during the main programme and may be subject to change.

5 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Arianna Tucci (Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

  • Arianna Tucci (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Fowzan ALKURAYA (King Faisal Specialist Hospital and Research Center)

    Group: Other
    Workplace: Other

20 genes

20 reviewed, 12 green

List Gene Reviews Mode of inheritance Details
20 genes
Green Green List (high evidence)
ADCY5
4 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Dyskinesia, familial, with facial myokymia, 606703
Green Green List (high evidence)
ATP2A1
4 reviews
3 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Brody myopathy 601003
Green Green List (high evidence)
CACNA1S
5 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hypokalemic periodic paralysis, type 1, 170400
Tags
  • treatable
Green Green List (high evidence)
CLCN1
5 reviews
3 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Myotonia congenita, recessive, 255700
  • Myotonia congenita, dominant, 160800
  • Myotonia levior, recessive
  • Myotonia Congenita
  • Hyperkalemic Periodic Paralysis
  • Myotonia
Green Green List (high evidence)
KCNA1
5 reviews
2 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Episodic ataxia/myokymia syndrome, 160120
  • Episodic Ataxia
  • Myokymia
  • Episodic Ataxia, Type 1
  • EA1
Green Green List (high evidence)
KCNJ2
5 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
Phenotypes
  • Hypokalemic Periodic Paralysis, Type 2
  • Episodic weakness
  • Periodic paralysis
  • ANDERSEN CARDIODYSRHYTHMIC PERIODIC PARALYSIS
  • Andersen syndrome
Green Green List (high evidence)
MT-ATP6
1 review
1 green
MITOCHONDRIAL
Sources
  • Expert Review Green
  • Expert Review
Green Green List (high evidence)
MT-ATP8
1 review
1 green
MITOCHONDRIAL
Sources
  • Expert Review Green
  • Expert Review
Green Green List (high evidence)
PYGM
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • McArdle disease, 232600
Green Green List (high evidence)
RYR1
1 review
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review
Green Green List (high evidence)
SCN4A
4 reviews
3 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
Phenotypes
  • Hyperkalemic periodic paralysis, type 2, 170500
  • Myasthenic syndrome, acetazolamide-responsive, 614198
  • Hypokalemic periodic paralysis, type 2, 613
  • Potassium-Aggravated Myotonia
  • Hyperkalemic Periodic Paralysis
  • Hypokalemic Periodic Paralysis
  • Thyrotoxic Periodic Paralysis, Susceptibility To, 2
  • Myotonia
  • Episodic weakness
Green Green List (high evidence)
SLC1A3
5 reviews
3 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Episodic ataxia, type 6, 612656
  • Episodic Ataxia
Amber Amber List (moderate evidence)
CACNA1A
4 reviews
3 red
Not set
Sources
  • Expert Review Amber
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Migraine, familial hemiplegic, 1, 141500
  • Episodic ataxia, type 2, 108500
  • Spinocerebellar ataxia 6, 183086
  • Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, 141500
  • Episodic Ataxia, Type 2
  • EA2
Amber Amber List (moderate evidence)
CACNB4
4 reviews
3 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Amber
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • {Epilepsy, juvenile myoclonic, susceptibility to, 6}, 607682
  • {Epilepsy, idiopathic generalized, susceptibility to, 9}, 607682
  • Episodic ataxia, type 5, 613855
  • Episodic Ataxia
Amber Amber List (moderate evidence)
KCNJ5
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Expert Review
Amber Amber List (moderate evidence)
KCNQ2
5 reviews
3 red
Not set
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Seizures, benign neonatal, 1, 121200
  • Myokymia, 121200
  • Epileptic encephalopathy, early infantile, 7, 613720
Red Red List (low evidence)
CNBP
6 reviews
1 red
Other - please specifiy in evaluation comments
Sources
  • Expert Review Red
  • Eligibility statement prior genetic testing
Phenotypes
  • Myotonia
  • MYOTONIC DYSTROPHY 2 (DM2)
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Red Red List (low evidence)
DMPK
5 reviews
2 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Eligibility statement prior genetic testing
Phenotypes
  • Myotonia
  • MYOTONIC DYSTROPHY 1 (DM1)
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Red Red List (low evidence)
HSPG2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Expert Review
Phenotypes
  • Schwartz-Jampel syndrome, type 1, 255800
Red Red List (low evidence)
KCNJ18
5 reviews
1 green 2 red
Not set
Sources
  • Expert Review Red
  • UKGTN
Phenotypes
  • Hypokalemic Periodic Paralysis, Type 1

2 STRs

2 reviewed, 0 green

List STR Reviews Mode of inheritance Details
2 STRss
Red Red List (low evidence)
CNBP_CCTG
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
Phenotypes
  • Myotonic dystrophy 2 602668
Tags
  • STR
Red Red List (low evidence)
DMPK_CTG
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
Phenotypes
  • Myotonic dystrophy 1 160900
Tags
  • STR

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