Description
Congenital myaesthenia eligibility statement:

Congenital myaesthenia inclusion criteria (29556)
- Patients at any age with fatigable weakness and fluctuating motor symptoms
- Clinical neurophysiology revealing a neuromuscular transmission defect (repetitive nerve stimulation, or Single fibre EMG)
- Review of patient data by CMS NHS Highly Specialised Services for Rare Diseases service

Congenital myaesthenia exclusion criteria (29556)
- Response to immunosuppressive treatment
- Presence of anti- AChR or MuSK antibodies
- Muscle biopsy indicative of mitochondrial disorder. Muscle biopsy giving clear indication of dystrophy or other muscle disorder

Prior genetic testing guidance (29556)
- 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.

Closing statement (29556)
These requirements will be kept under continual review during the main programme and may be subject to change.

2 reviewers

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • David Beeson (Oxford University)

    Group: Other
    Workplace: Research lab

29 Entities

29 reviewed, 20 green

List Entity Reviews Mode of inheritance Details
29 Entitiess
Green Green List (high evidence)
AGRN
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Congenital myasthenic syndrome
  • Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, 615120
Tags
Green Green List (high evidence)
CHAT
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Myasthenic syndrome, congenital, 6, presynaptic, 254210
  • Congenital myasthenics sndrome associated with episodic apnea
  • CMS-EA
Tags
Green Green List (high evidence)
CHRNA1
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital Myasthenic Syndrome, Dominant/Recessive
  • Myasthenic syndrome, congenital, 1A, slow-channel, 601462
  • Myasthenic syndrome, congenital, 1B, fast-channel, 608930
  • Slow channel myasthenic syndrome
  • fast channel myasthenic syndrome
  • Acetylcholine receptor deficiency syndrome
Tags
Green Green List (high evidence)
CHRNB1
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • ?Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency, 616314
  • Myasthenic syndrome, congenital, 2A, slow-channel, 616313
  • Slow channel myasthenic syndrome
  • fast channel myasthenic syndrome
  • Acetylcholine receptor deficiency syndrome
  • Myasthenic syndrome, slow-channel congenital, 601462
  • Congenital Myasthenic Syndrome, Dominant/Recessive
Tags
  • deletions
Green Green List (high evidence)
CHRND
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital Myasthenic Syndrome, Dominant/Recessive
  • Myasthenic syndrome, slow-channel congenital, 601462
  • Slow channel myasthenic syndrome
  • fast channel myasthenic syndrome
  • Acetylcholine receptor deficiency syndrome
  • ?Myasthenic syndrome, congenital, 3A, slow-channel, 616321
  • ?Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency, 616323
  • Myasthenic syndrome, congenital, 3B, fast-channel, 616322
Tags
Green Green List (high evidence)
CHRNE
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital Myasthenic Syndrome, Dominant/Recessive
  • Myasthenic syndrome, slow-channel congenital, 601462
  • Myasthenic syndrome, congenital, 4A, slow-channel, 605809
  • Myasthenic syndrome, congenital, 4B, fast-channel, 616324
  • Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931
  • Slow channel myasthenic syndrome
  • fast channel myasthenic syndrome
  • Acetylcholine receptor deficiency syndrome
  • Reduced channel conductance syndrome
Tags
Green Green List (high evidence)
CHRNG
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Myasthenia gravis, neonatal transient
  • Neonatal congenital myasthenia
  • escobar syndrome
  • fetal akinesia deformation sequence syndrome/FADS
  • multiple pterygium syndrome/MPS
Tags
Green Green List (high evidence)
COL13A1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Literature
Phenotypes
  • Congenital myasthenic syndrome type 19
  • Myasthenic syndrome, congenital, 19, 616720
Tags
Green Green List (high evidence)
COLQ
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Congenital Myasthenic Syndrome, Recessive
  • Congenital myasthenic syndrome with endplate acetylcholinesterase deficiency
  • Myasthenic syndrome, congenital, 5, 603034
Tags
  • treatable
Green Green List (high evidence)
DOK7
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Myasthenic syndrome, congenital, 10, 254300
  • Myasthenia, limb-girdle, familial
  • Limb girdle congenital myasthenic syndrome
Tags
  • treatable
Green Green List (high evidence)
DPAGT1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital disorder of glycosylation, type Ij, 608093
  • Myasthenic syndrome, congenital, 13, with tubular aggregates, 614750
  • Limb girdle congenital myasthenic
  • tubular aggregates
  • congenital disorder of glycosylation type Ij (CDG-IJ)
Tags
Green Green List (high evidence)
GFPT1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital Myasthenic Syndrome, Recessive
  • Myasthenia, congenital, 12, with tubular aggregates, 610542
  • Limb-girdle congenital myasthenic syndrome
  • tubular aggregates
Tags
Green Green List (high evidence)
GMPPB
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Congenital Myasthenic Syndrome
  • muscular dystrophy-dystroglycanopathy
  • congenital muscular dystrophy with mental retardation
  • GMPPB-CMS
  • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 with features of congenital myasthenic syndrome
  • MDDGC14 with features of CMS
Tags
Green Green List (high evidence)
LRP4
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Congenital myasthenic syndrome
  • Myasthenic syndrome, congenital, 17, 616304
Tags
Green Green List (high evidence)
MUSK
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency, 616325
  • Congenital Myasthenic Syndrome, Recessive
  • Congenital myasthenic syndrome
Tags
  • deletions
Green Green List (high evidence)
PLEC
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Congenital myasthenic syndrome
  • Plectin deficiency
  • myasthenic syndrome
  • Congenital myasthenic syndrome associatedwith epidermolysis bullosa (EBS)
Tags
  • monogenic-polygenic
Green Green List (high evidence)
RAPSN
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital Myasthenic Syndrome, Recessive
  • Congenital myasthenic syndrome
  • Myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency, 616326
  • acute respiratory crises
  • late and early onset
Tags
Green Green List (high evidence)
SCN4A
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Myasthenic syndrome, congenital, 16, 614198
  • Congenital Myasthenic Syndrome, Recessive
  • congenital myasthenic syndromes
Tags
Green Green List (high evidence)
SLC18A3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Congenital myasthenic syndrome
  • ophthalmopleggia and apnea
  • Myasthenic syndrome, congenital, 21, presynaptic, 617239
Tags
Green Green List (high evidence)
SLC5A7
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Congenital myasthenic syndrome
  • Hereditory motor neuropathy
  • Myasthenic syndrome, congenital, 20, presynaptic, 617143
Tags
Amber Amber List (moderate evidence)
ALG2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Congenital myasthenic syndromes
  • Myasthenic syndrome, congenital, 14, with tubular aggregates, 616228
  • Congenital disorder of glycosylation CDG type Ii, 607906
Tags
Amber Amber List (moderate evidence)
MYO9A
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • congenital myasthenic syndrome
  • CMS
Tags
Amber Amber List (moderate evidence)
VAMP1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Congenital myasthenic syndrome
  • presynaptic CMS
Tags
  • watchlist
Red Red List (low evidence)
ALG14
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Red
Phenotypes
  • Congenital myasthenic syndrome
  • ?Myasthenic syndrome, congenital, 15, without tubular aggregates, 616227
Tags
Red Red List (low evidence)
LAMB2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Congenital myasthenic syndrome
  • congenital myasthenic syndrome (CMS) associated with congenital nephrosis and ocular malformations
  • synaptic congenital myasthenic syndrome
Tags
Red Red List (low evidence)
PREPL
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • myasthenic syndrome
  • congenital myasthenic syndrome with pre- and postsynaptic features and growth hormone deficiency
  • ?Myasthenic syndrome, congenital, 22, 616224
Tags
  • deletions
  • polygenic
  • treatable
Red Red List (low evidence)
SNAP25
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Other
Phenotypes
  • ?Myasthenic syndrome, congenital, 18, 616330
Tags
Red Red List (low evidence)
SYT2
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Myasthenic syndrome, congenital, 7, presynaptic, 616040
Tags
No list No list
GRN
1 review
Not set
Sources
  • Expert Review Removed
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Frontotemporal lobar degeneration with ubiquitin-positive inclusions, 607485Myasthenia, limb-girdle, familial, 254300
Tags

Major version comments

Downloads

Download lists

Download Version