Description
Early onset or familial intestinal pseudo obstruction inclusion criteria (41880)
A. Chronic visceral dilatation including part or all of the small intestine (chronic intestinal pseudo-obstruction)

AND one of:

B1. Diagnosis within first year of life (majority will have symptoms from the neonatal period)
B2. Diagnosis at any age but with at least one first or second degree relative with a diagnosis of either IPO or another severe digestive motility disorder (enteric dysmotility; oesophageal achalasia, megacolon, megarectum).

Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease.

In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Early onset or familial intestinal pseudo obstruction exclusion criteria (41880)
Proven mitochondrial myopathy (MNGIE) [by MRI / muscle biopsy in suspected cases]
Proven early onset secondary cause e.g. muscular dystrophy or cystic fibrosis [with relevant testing if clinical suspicion]

Prior genetic testing guidance (41880)
- 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.

Early onset or familial intestinal pseudo obstruction prior genetic testing genes (41880)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 No genes specified

Closing statement (41880)
These requirements will be kept under continual review during the main programme and may be subject to change.

6 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Richard Scott (Genomics England Curator)

    Group: Other
    Workplace: Genomics England

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Neil shah (GOSH)

    Group: Other NHS organisation
    Workplace: NHS clinical service

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Helen Brittain (Genomics England Curator)

    Group: Other
    Workplace: Other

26 genes

26 reviewed, 15 green

List Gene Reviews Mode of inheritance Details
26 genes
Green Green List (high evidence)
ACTG2
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Visceral myopathy 155310
Green Green List (high evidence)
ATRX
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
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Alpha-thalassemia/mental retardation syndrome 301040
Green Green List (high evidence)
CLMP
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Green
Phenotypes
  • Congenital short bowel syndrome 615237
Green Green List (high evidence)
DES
2 reviews
2 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Myopathy, myofibrillar, 1 601419
Green Green List (high evidence)
DMD
4 reviews
1 green 1 red
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Duchenne muscular dystrophy 310200
Tags
  • gene-therapy-trial
Green Green List (high evidence)
FLNA
2 reviews
2 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Intestinal pseudoobstruction, neuronal 300048
  • Congenital short bowel syndrome 300048
Green Green List (high evidence)
IDS
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
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Mucopolysaccharidosis II 309900
Green Green List (high evidence)
POLG
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Mitochondrial DNA depletion syndrome 4B (MNGIE type) 613662
Green Green List (high evidence)
RET
3 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Hirschsprung disease, susceptibility to, 1} 142623
Tags
  • polygenic
Green Green List (high evidence)
RRM2B
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Mitochondrial DNA depletion syndrome 8B (MNGIE type) 612075
  • Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy)
Green Green List (high evidence)
SAMD9
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • MIRAGE syndrome 617053
Tags
  • missense
Green Green List (high evidence)
SCN11A
3 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Neuropathy, hereditary sensory and autonomic, type VII 615548
Green Green List (high evidence)
SOX10
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Waardenburg syndrome, type 4C 613266
Green Green List (high evidence)
TMEM70
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 614052
Green Green List (high evidence)
TYMP
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
Phenotypes
  • Mitochondrial DNA depletion syndrome 1 (MNGIE type) 603041
Amber Amber List (moderate evidence)
GDNF
2 reviews
1 green
Unknown
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • {Hirschsprung disease, susceptibility to, 3} 613711
Tags
  • polygenic
Amber Amber List (moderate evidence)
L1CAM
3 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hydrocephalus with congenital idiopathic intestinal pseudoobstruction 307000
Amber Amber List (moderate evidence)
PTEN
2 reviews
Not set
Sources
  • Expert Review Amber
Phenotypes
  • Bannayan-Riley-Ruvalcaba syndrome 153480
Red Red List (low evidence)
CAVIN1
3 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Lipodystrophy, congenital generalized, type 4 613327
Red Red List (low evidence)
COG7
2 reviews
1 red
Unknown
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Red
Phenotypes
  • Congenital disorder of glycosylation, type IIe 608779
Red Red List (low evidence)
DMPK
2 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Red
  • Emory Genetics Laboratory
Phenotypes
  • Myotonic dystrophy 1 160900
Tags
  • nucleotide-repeat-expansion
Red Red List (low evidence)
EVC2
4 reviews
1 green 1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Ellis-van Creveld syndrome, with chronic intestinal pseudo-obstruction 225500
Red Red List (low evidence)
MT-TK
3 reviews
2 red
MITOCHONDRIAL
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY SYNDROME
Red Red List (low evidence)
SGO1
4 reviews
1 green 2 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Other
  • Expert Review Red
Phenotypes
  • Chronic atrial and intestinal dysrhythmia 616201
Tags
  • founder-effect
Red Red List (low evidence)
SMO
2 reviews
2 red
Other - please specify in evaluation comments
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Curry-Jones syndrome, somatic mosaic 601707
Tags
  • mosaicism
Red Red List (low evidence)
TTC7A
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Gastrointestinal defects and immunodeficiency syndrome 243150

1 STR

1 reviewed, 0 green

List STR Reviews Mode of inheritance Details
1 STRs
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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