Anophthalmia or microphthalmia (Version 1.51)

Description

Relevant diseases:

- Anophthalmia/microphthalmia


Anophthalmia (clinical absence of the eye) and severe microphthalmia (congenital reduction in the overall size of the globe) represent clinically significant inborn errors of early development.

Anophthalmia inclusion criteria (29638)
- Unilateral or bilateral anophthalmia or microphthalmia

Anophthalmia exclusion criteria (29638)

Prior genetic testing guidance (29638)
- 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.

Anophthalmia prior genetic testing genes (29638)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - Genome-wide copy number variation (e.g. aCGH, SNP array or other genomic microarray)
 - SOX2, OTX2 (severe, bilateral cases)

Closing statement (29638)
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

13 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
David FitzPatrick (University of Edinburgh)

Group: GeCIP domain
Workplace: Research lab
Richard Scott (Genomics England Curator)

Group: Other
Workplace: Other
Damian Smedley (Genomics England Curator)

Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Owen Siggs (Flinders University)

Group: Other
Workplace: Research lab
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other
Zornitza Stark (Australian Genomics)

Group: Other
Workplace: Other clinical service
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

Group: Other NHS organisation
Workplace: NHS diagnostic lab
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other

63 Entities

63 reviewed, 37 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 63 Entitiess
Green Green List (high evidence)	ALDH1A3	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, isolated 8, 615113 Tags
Green Green List (high evidence)	BCOR	2 reviews 1 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, syndromic 2, 300166 Tags
Green Green List (high evidence)	BMP4	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes BMP4-Related Syndromic Microphthalmia Microphthalmia, syndromic 6, 607932Orofacial cleft 11, 600625 Tags
Green Green List (high evidence)	CAPN15	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Oculogastrointestinal neurodevelopmental syndrome, OMIM:619318 Microphthalmia, HP:0000568 Coloboma, HP:0000589 Tags
Green Green List (high evidence)	COL4A1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	FAT1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes facial dysmorphism colobomatous microphthalmia ptosis syndactyly with or without nephropathy Tags gene-checked
Green Green List (high evidence)	FOXC1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	FOXE3	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Anterior segment dysgenesis 2, multiple subtypes, OMIM:610256 Ocular anterior segment dysgenesis, HP:0007700 Tags
Green Green List (high evidence)	FRAS1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	FREM1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	FREM2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	GRIP1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	HCCS	3 reviews 1 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, syndromic 7, 309801 Tags
Green Green List (high evidence)	KMT2D	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes microphthalmia Kabuki syndrome 1, 147920 Tags
Green Green List (high evidence)	MAB21L2	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, syndromic 14, 615877 Tags
Green Green List (high evidence)	MFRP	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, isolated 5, 611040 Isolated Microphthalmia Tags
Green Green List (high evidence)	MYRF	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Nanophthalmos high hyperopia Tags
Green Green List (high evidence)	OTX2	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes OTX2-Related Syndromic Microphthalmia Microphthalmia, syndromic 5, 610125 severe, bilateral cases Tags
Green Green List (high evidence)	PAX2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes 120330 Tags
Green Green List (high evidence)	PAX6	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Phenotypes Anophthalmia Tags
Green Green List (high evidence)	PITX2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Green Tags
Green Green List (high evidence)	PRSS56	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, isolated 6, 613517 Tags
Green Green List (high evidence)	RAB18	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Warburg Micro Syndrome Warburg micro syndrome 3, 614222 Tags
Green Green List (high evidence)	RAB3GAP1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Warburg Micro Syndrome Warburg micro syndrome 1, 600118 Tags
Green Green List (high evidence)	RAB3GAP2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Martsolf syndrome 1, OMIM:212720 Warburg micro syndrome 2, OMIM:614225 Tags
Green Green List (high evidence)	RARB	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, syndromic 12, 615524 Tags
Green Green List (high evidence)	RAX	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Phenotypes Microphthalmia, isolated 3, OMIM:611038 isolated microphthalmia 3, MONDO:0012604 Tags
Green Green List (high evidence)	SHH	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Holoprosencephaly-3, 142945Single median maxillary central incisor, 147250Microphthalmia with coloboma 5, 611638Schizencephaly, 269160 Tags
Green Green List (high evidence)	SIX6	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Optic disc anomalies with retinal and/or macular dystrophy, OMIM:212550 Tags
Green Green List (high evidence)	SMO	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Curry-Jones syndrome, somatic mosaic 601707 Tags mosaicism somatic
Green Green List (high evidence)	SMOC1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia with limb anomalies, 206920 Tags
Green Green List (high evidence)	SOX2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Microphthalmia, syndromic 3, 206900Optic nerve hypoplasia and abnormalities of the central nervous system, 206900 severe, bilateral cases Tags
Green Green List (high evidence)	STRA6	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 Syndromic Microphthalmia, Recessive Microphthalmia, syndromic 9, 601186Microphthalmia, isolated, with coloboma 8, 601186 Tags
Green Green List (high evidence)	TBC1D20	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Warburg micro syndrome 4, 615663 Tags
Green Green List (high evidence)	TENM3	2 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, syndromic 15, OMIM:615145 ?Microphthalmia, isolated, with coloboma 9, OMIM:615145 Microphthalmia, isolated, with coloboma 9, MONDO:0014059 Tags
Green Green List (high evidence)	TMEM98	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Nanophthalmos 4, OMIM:615972 Nanophthalmos 4, MONDO:0014426 Tags
Green Green List (high evidence)	VSX2	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 Microphthalmia with coloboma 3 Tags
Amber Amber List (moderate evidence)	C16orf62	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes 3C/Ritscher-Schinzel-like syndrome Tags new-gene-name
Amber Amber List (moderate evidence)	PLK4	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM:616171 microcephaly and chorioretinopathy 2, MONDO:0014516 Tags watchlist
Amber Amber List (moderate evidence)	TUBGCP4	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Microcephaly and chorioretinopathy, autosomal recessive, 3, 616335 Tags watchlist
Red Red List (low evidence)	ABCB6	1 review 1 red	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, isolated, with coloboma 7, 614497 Tags
Red Red List (low evidence)	B3GLCT	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Tags
Red Red List (low evidence)	BMPR1A	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	CYP1B1	1 review 1 red	Not set	Sources Emory Genetics Laboratory Tags
Red Red List (low evidence)	DDB1	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	DDB2	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	ERCC1	2 reviews 1 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes Cerebrooculofacioskeletal syndrome 4, 610758 Tags
Red Red List (low evidence)	ERCC2	2 reviews 1 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes Xeroderma pigmentosum, group D, 278730Trichothiodystrophy, 601675Cerebrooculofacioskeletal syndrome 2, 610756 Tags
Red Red List (low evidence)	ERCC3	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	ERCC4	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	ERCC5	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	ERCC6	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Cerebrooculofacioskeletal Syndrome Cockayne syndrome, type B, 133540Cerebrooculofacioskeletal syndrome 1, 214150De Sanctis-Cacchione syndrome, 278800{Macular degeneration, age-related, susceptibility to 5}, 613761UV-sensitive syndrome 1, 600630{Lung cancer, susceptibility to}, 211980 Tags
Red Red List (low evidence)	ERCC8	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	GDF3	1 review 1 red	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Klippel-Feil syndrome 3, autosomal dominant, 613702 Tags
Red Red List (low evidence)	GDF6	1 review 1 red	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Klippel-Feil syndrome 1, autosomal dominant, 118100 Tags
Red Red List (low evidence)	GTF2H5	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	HDAC6	1 review	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, andmicrophthalmia, 300863 Tags
Red Red List (low evidence)	MPLKIP	2 reviews 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	PITX3	1 review 1 red	Not set	Sources Emory Genetics Laboratory Tags
Red Red List (low evidence)	POLH	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	VAX1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Microphthalmia, syndromic 11, 614402 Tags
Red Red List (low evidence)	XPA	1 review 1 red	Not set	Sources UKGTN Tags
Red Red List (low evidence)	XPC	1 review 1 red	Not set	Sources UKGTN Tags

Major version comments

10th May 2016. Promoted to v1 based on review of known expert reviews and literature evidence

Anophthalmia or microphthalmia (Version 1.51)

13 reviewers

63 Entities

63 reviewed, 37 green

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Tags

2 reviews

Sources

Phenotypes

Tags

3 reviews

Sources

Tags

3 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Tags

2 reviews

Sources

Tags

2 reviews

Sources

Tags

2 reviews

Sources

Tags

3 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

3 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources

Phenotypes

Tags

2 reviews

Sources