Description
Paediatric motor neuronopathies eligibility statement:

Relevant diseases:

- Brown-Vialetto-Van Laere syndrome
- Spinal muscular atrophy with respiratory distress
- Fazio-Londe syndrome

Paediatric motor neuronopathies inclusion criteria (29519)
- Bulbar palsy +/- sensorineural deafness, visual impairment, seizures, motor and/or global developmental delay
- Congenital or presentation in early childhood most commonly (presentation can occur in adult life, but is rare)
- Full neurometabolic screen completed with normal/inconclusive findings
- EMG consistent with bulbar palsy +/- evidence of more extensive motor neuron involvement

Paediatric motor neuronopathies exclusion criteria (29519)

Prior genetic testing guidance (29519)
- 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 (29519)
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

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

  • Dragana Josifova (Guy's and St. Thomas' NHS Trust)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Arianna Tucci (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Pinki Munot (Consultant )

    Group: Other NHS organisation
    Workplace: NHS clinical service

39 genes

39 reviewed, 15 green

List Gene Reviews Mode of inheritance Details
39 genes
Green Green List (high evidence)
AR
4 reviews
2 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Androgen insensitivity, 300068Spinal and bulbar muscular atrophy of Kennedy, 313200Androgen insensitivity, partial, with or without breast cancer, 312300{Prostate cancer, susceptibility to}, 176807Hypospadias 1, X-linked, 300633
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Green Green List (high evidence)
ASAH1
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Spinal muscular atrophy with progressive myoclonic epilepsy, 159950
Green Green List (high evidence)
BICD2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spinal muscular atrophy, lower extremity-predominant, 2, AD, 615290 -3
Green Green List (high evidence)
CHCHD10
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spinal muscular atrophy, Jokela type 615048
Green Green List (high evidence)
DYNC1H1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spinal muscular atrophy, lower extremity-predominant, AD, 158600
Green Green List (high evidence)
EXOSC3
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Pontocerebellar hypoplasia, type 1B 614678
Green Green List (high evidence)
IGHMBP2
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
Phenotypes
  • Spinal muscular atrophy with respiratory distress, 604320
Green Green List (high evidence)
SLC52A2
4 reviews
3 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Brown-Vialetto-Van Laere syndrome 2, 614707
Green Green List (high evidence)
SLC52A3
3 reviews
3 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Brown-Vialetto-Van Laere syndrome 1, 211530
Green Green List (high evidence)
SMN1
4 reviews
3 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Spinal muscular atrophy-1, 253300
Tags
  • gene-therapy-trial
  • cnv
Green Green List (high evidence)
SPG11
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
Phenotypes
  • Amyotrophic lateral sclerosis 5, juvenile 602099
Green Green List (high evidence)
TRIP4
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Spinal muscular atrophy with congenital bone fractures 1 616866
Green Green List (high evidence)
TRPV4
3 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Expert
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Distal Congenital Nonprogressive Spinal Muscular Atrophy
  • Brachyolmia type 3, 113500
Green Green List (high evidence)
UBA1
2 reviews
2 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Infantile Spinal Muscular Atrophy, X-Linked
  • Spinal muscular atrophy, X-linked 2, infantile, 301830
Green Green List (high evidence)
VRK1
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Pontocerebellar hypoplasia type 1A 607596
Amber Amber List (moderate evidence)
ALS2
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Amber
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • juvenile amyotrophic lateral sclerosis-2, 205100
Amber Amber List (moderate evidence)
ATP7A
2 reviews
Not set
Sources
  • Expert Review Amber
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Menkes disease, 309400Occipital horn syndrome, 304150Spinal muscular atrophy, distal, X-linked 3, 300489
Amber Amber List (moderate evidence)
EXOSC8
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
  • UKGTN
Phenotypes
  • Pontocerebellar hypoplasia, type 1C 616081
Amber Amber List (moderate evidence)
HSPB1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Expert
Amber Amber List (moderate evidence)
HSPB8
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Expert
Phenotypes
  • Neuropathy, distal hereditary motor, type IIA 158590
Amber Amber List (moderate evidence)
REEP1
3 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • ?Neuronopathy, distal hereditary motor, type VB 614751
Amber Amber List (moderate evidence)
SETX
3 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Amber
Phenotypes
  • Amyotrophic lateral sclerosis 4, juvenile 602433
Amber Amber List (moderate evidence)
VAPB
3 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Spinal muscular atrophy, late-onset, Finkel type 182980
  • Amyotrophic lateral sclerosis 8 608627
Red Red List (low evidence)
AARS
3 reviews
2 red
Not set
Sources
  • Expert
  • Expert Review Red
Red Red List (low evidence)
BSCL2
2 reviews
1 green
Not set
Sources
  • Expert Review Red
  • Expert
Red Red List (low evidence)
DCTN1
1 review
Not set
Sources
  • Expert Review Red
  • Expert
Red Red List (low evidence)
DMPK
2 reviews
1 red
Not set
Sources
  • Expert Review Red
  • Emory Genetics Laboratory
Phenotypes
  • spinal muscular atrophy, myotonic dystrophy (type 1), Prader-Willi syndrome, Angelman syndrome, and maternal UPD 14.
Tags
  • currently-ngs-unreportable
  • nucleotide-repeat-expansion
Red Red List (low evidence)
DNAJB2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Red
  • Expert
Phenotypes
  • Spinal muscular atrophy, distal, autosomal recessive, 5, 614881
Red Red List (low evidence)
FBXO38
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Red
Phenotypes
  • Neuronopathy, distal hereditary motor, type IID 615575
Red Red List (low evidence)
GARS
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Expert
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Distal Spinal Muscular Atrophy
Red Red List (low evidence)
HSPB3
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert
  • Expert Review Red
Phenotypes
  • ?Neuronopathy, distal hereditary motor, type IIC 613376
Red Red List (low evidence)
MEG3
2 reviews
Not set
Sources
  • Expert Review Red
Tags
  • locus-type-rna-long-non-coding
Red Red List (low evidence)
PLEKHG5
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Red
  • Expert
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Distal Spinal Muscular Atrophy
  • Spinal muscular atrophy, distal, autosomal recessive, 4, 611067
Red Red List (low evidence)
SIGMAR1
2 reviews
2 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • Literature
Phenotypes
  • ?Amyotrophic lateral sclerosis 16, juvenile 614373
Red Red List (low evidence)
SLC52A1
2 reviews
2 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • UKGTN
Red Red List (low evidence)
SLC5A7
2 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
  • UKGTN
Phenotypes
  • Neuronopathy, distal hereditary motor, type VIIA 158580
Red Red List (low evidence)
SNRPN
4 reviews
1 red
Other - please specifiy in evaluation comments
Sources
  • Expert Review Red
  • Emory Genetics Laboratory
Phenotypes
  • Prader-Willi syndrome 176270
Tags
  • currently-ngs-unreportable
Red Red List (low evidence)
SYT2
2 reviews
Not set
Sources
  • Expert Review Red
  • Expert
Red Red List (low evidence)
UBQLN1
2 reviews
2 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Brown-Vialetto-Van Laere syndrome/ atypical motor neurone disease

2 STRs

2 reviewed, 2 green

List STR Reviews Mode of inheritance Details
2 STRss
Green Green List (high evidence)
AR_CAG
2 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert list
  • Expert Review Green
Phenotypes
  • Spinal and bulbar muscular atrophy or Kennedy diseases 313200
Tags
  • STR
Green Green List (high evidence)
DMPK_CTG
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Myotonic dystrophy 1 160900
Tags
  • STR

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