Description
Cerebellar hypoplasia eligibility statement:

Cerebellar hypoplasia inclusion criteria (36515)
•	Cerebellar or ponto-cerebellar hypoplasia on MRI brain scan

Cerebellar hypoplasia exclusion criteria (36515)
•	Findings characteristic of Joubert syndrome (in which case recruit to Joubert syndrome category)
•	Known genetic cause
•	Evidence of causative prenatal infection such as CMV (this usually causes more widespread brain abnormalities such as calcification not just cerebellar hypoplasia)

Prior genetic testing guidance (36515)
- 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.

Cerebellar hypoplasia prior genetic testing genes (36515)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 -	Gene panel including ITPR1, SPTBN2, KCNC3, CASK, OPHN1

Closing statement (36515)
These requirements will be kept under continual review during the main programme and may be subject to change.

7 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • emma baple (Genomics England Curator)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Arianna Tucci (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Helen Brittain (Genomics England Curator)

    Group: Other
    Workplace: Other

62 genes

61 reviewed, 42 green

List Gene Reviews Mode of inheritance Details
62 genes
Green Green List (high evidence)
LARGE1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Congenital Muscular Dystrophy, alpha-dystroglycan related
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
ADGRG1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Expert Review Green
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Polymicrogyria, bilateral frontoparietal 606854
Green Green List (high evidence)
AMPD2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Other
Phenotypes
  • pontocerebellar hypoplasia type 9, 615809
Green Green List (high evidence)
B3GALNT2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies typeA 11
  • congenital muscular dystrophies
Green Green List (high evidence)
CACNA1G
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 42 616795
Tags
  • missense
Green Green List (high evidence)
CASK
2 reviews
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • UKGTN
  • Other
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Mental retardation and microcephaly with pontine and cerebellar hypoplasia
  • FG syndrome 4
  • Mental retardation, with or without nystagmus
  • Pontocerebellar Hypoplasia
  • Mental retardation and microcephaly with pontine and cerebellar hypoplasia, 300749
  • FG syndrome 4, 300422
  • Mental retardation, with or without nystagmus, 300422
Green Green List (high evidence)
CHMP1A
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 8
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia,type 8,614961
Green Green List (high evidence)
CLP1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 10
  • Pontocerebellar Hypoplasia
Green Green List (high evidence)
CWF19L1
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 17, 616127
Green Green List (high evidence)
DKC1
1 review
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Emory Genetics Laboratory
Phenotypes
  • X-linked dyskeratosis congenita
Green Green List (high evidence)
EXOSC3
0 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 1B
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia, type 1B, 614678
Green Green List (high evidence)
FKRP
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
FKTN
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Fukuyama congenital muscular dystrophy
  • Fukuyama Congenital Muscular Dystrophy
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
GMPPB
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
ISPD
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Congenital Muscular Dystrophy, alpha-dystroglycan related
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
ITPR1
2 reviews
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Eligibility statement prior genetic testing
Phenotypes
  • Spinocerebellar ataxia 15
  • Spinocerebellar ataxia 29, congenital nonprogressive
  • Gillespie syndrome 206700
Green Green List (high evidence)
KCNC3
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • UKGTN
  • Other
  • Eligibility statement prior genetic testing
Phenotypes
  • Spinocerebellar ataxia 13
Green Green List (high evidence)
OPHN1
2 reviews
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Other
  • Eligibility statement prior genetic testing
Phenotypes
  • Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance
  • XLMR with Cerebellar Hypoplasia and Distinctive Facial Appearance
  • Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486
Green Green List (high evidence)
POMGNT1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
Phenotypes
  • Congenital Muscular Dystrophy, alpha-dystroglycan related
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
POMGNT2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies type
Green Green List (high evidence)
POMT1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670
Green Green List (high evidence)
POMT2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • UKGTN
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Green Green List (high evidence)
PTF1A
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Pancreatic and cerebellar agenesis, 609069
Green Green List (high evidence)
RARS2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 6
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia, type 6, 611523
Green Green List (high evidence)
RELN
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Emory Genetics Laboratory
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Lissencephaly 2, 257320
Green Green List (high evidence)
ROBO3
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Gaze palsy, familial horizontal, with progressive scoliosis, 1 607313
Green Green List (high evidence)
SEPSECS
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 2D
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia type 2D, 613811
Green Green List (high evidence)
SNX14
1 review
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Literature
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 20, 616354
Green Green List (high evidence)
SPTBN2
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Other
  • Eligibility statement prior genetic testing
Phenotypes
  • Spinocerebellar ataxia 5 (AD)
  • Spinocerebellar ataxia, autosomal recessive 14 (AR)
Green Green List (high evidence)
TINF2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Dyskeratosis congenita, autosomal dominant 3 613990
Green Green List (high evidence)
TMEM5
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type
Tags
  • new-gene-name
Green Green List (high evidence)
TOE1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Pontocerebellar hypoplasia, type 7 614969
Green Green List (high evidence)
TSEN2
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Pontocerebellar Hypoplasia type 2B
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia type 2B,612389
Green Green List (high evidence)
TSEN34
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 2C
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia type 2C,612390
Green Green List (high evidence)
TSEN54
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 5
  • Pontocerebellar Hypoplasia type 2A
  • Pontocerebellar Hypoplasia type 4
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia type 2A, 277470
  • Pontocerebellar hypoplasia type 4, 225753
Green Green List (high evidence)
TUBA1A
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • Literature
Phenotypes
  • Lissencephaly 3 6,1603
Green Green List (high evidence)
TUBA8
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Polymicrogyria with optic nerve hypoplasia, 613180
Green Green List (high evidence)
TUBB2B
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Literature
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • complex cortical dysplasia with other brain malformations-7 , 610031
Green Green List (high evidence)
TUBB3
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
Phenotypes
  • Cortical dysplasia, complex, with other brain malformations 1 614039
Green Green List (high evidence)
VLDLR
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, 224050
  • Cerebellar Hypoplasia
Green Green List (high evidence)
VRK1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 1A
  • Pontocerebellar Hypoplasia with infantile SMA
  • Pontocerebellar Hypoplasia with anterior horn cell disease
  • Pontocerebellar Hypoplasia
  • Pontocerebellar hypoplasia type 1A,607596
Green Green List (high evidence)
WDR81
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
  • UKGTN
Phenotypes
  • Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 2, 610185
Amber Amber List (moderate evidence)
ATP8A2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 615268
Amber Amber List (moderate evidence)
B4GAT1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • UKGTN
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13, 615287
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), typeA, 13, 615287
Amber Amber List (moderate evidence)
CA8
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3 613227
Amber Amber List (moderate evidence)
DAG1
1 review
1 green
Not set
Sources
  • Expert Review Amber
  • Emory Genetics Laboratory
Phenotypes
  • congenital muscular dystrophies
Amber Amber List (moderate evidence)
DCC
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Gaze palsy, familial horizontal, with progressive scoliosis 2, 617542
Tags
  • watchlist
  • structural-variant
Amber Amber List (moderate evidence)
PHGDH
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Neu-Laxova syndrome 1, 256520
Amber Amber List (moderate evidence)
TERT
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • UKGTN
  • Literature
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • dyskeratosis congenita-2
Amber Amber List (moderate evidence)
VPS53
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • UKGTN
Phenotypes
  • Pontocerebellar Hypoplasia type 2E
  • Pontocerebellar Hypoplasia
Red Red List (low evidence)
BRF1
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Cerebellofaciodental syndrome 616202
Red Red List (low evidence)
CDK5
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Lissencephaly 7 with cerebellar hypoplasia 616342
Red Red List (low evidence)
EXOSC8
1 review
1 red
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Pontocerebellar hypoplasia,type 1C, 616081
Red Red List (low evidence)
FRMD4A
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia, 616819
Red Red List (low evidence)
PCLO
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
Phenotypes
  • Pontocerebellar Hypoplasia type 3
Red Red List (low evidence)
PI4KA
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis , 616531
Red Red List (low evidence)
PMPCA
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 2 213200 AR
Red Red List (low evidence)
POMK
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
  • UKGTN
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 615249
Red Red List (low evidence)
SMPD4
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Research
Phenotypes
  • cerebellar hypoplasia, hypomyelination, microcephaly, arthrogryposis, diabetes
Tags
  • watchlist
Red Red List (low evidence)
STUB1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 16 615768
Red Red List (low evidence)
TSEN15
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Literature
Phenotypes
  • Pontocerebellar hypoplasia, type 2F 617026
Red Red List (low evidence)
TUBB
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Literature
Phenotypes
  • Cortical dysplasia, complex, with other brain malformations 6, 615771

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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