Coarse facial features including Coffin-Siris-like disorders (Version 0.58)

This Panel is marked as Internal

Description

Inclusion criteria:
- Coarse facial features warranting further investigation -particularly those with other medical problems, additional dysmorphic facial features or intellectual disability, AND
- Previous investigations to exclude metabolic disorder including a minimum of plasma amino acids, urine organic acids and urine GAGs, AND

Exclusion criteria:
- Known genetic aetiology
- Untreated congenital hypothyroidism
- Metabolic investigations indicative of likely inborn error of metabolism (these
individuals should follow a metabolic pathway of investigation and
recruitment)
- Clinical features of an insulin resistance / lipodystrophy disorder, RASopathy or
overgrowth disorder (these individuals should be investigated and recruited to the relevant specific rare disorder)

Prior Genetic Testing:
- Results should have been reviewed for all genetic tests undertaken. This includes review of available exome sequencing data, but where this is the case can be limited to genes specified within disease-relevant in silico panels. The patient is not eligible if a pathogenic variant has been identified in any gene related to their phenotype.
- Standard local genetic testing and nationally commissioned testing for this phenotype should have been completed AND
- Testing should be undertaken for any individual gene for which diagnostic yield is >10% for this phenotype AND
- The following specific gene tests are advised as a means of limiting the re- discovery of recognised pathogenic variants that could be more efficiently identified through the existing catalogue of UKGTN tests:
o Guided by phenotype. There should be a low threshold for Ras-MAPK gene testing, and 11p15 methylation analysis should be considered
o If clinical diagnosis of Pallister-Killian syndrome is considered likely, a skin biopsy for chromosome analysis should be performed prior to recruitment

These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

4 reviewers

Alice Gardham (North West Thames Genetics)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
alisdair mcneill (Sheffield childrens hospital)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Alice Gardham (Genomics England)

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

Group: Other
Workplace: Other

38 Entities

38 reviewed, 10 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 38 Entitiess
Green Green List (high evidence)	ABCC9	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Hypertrichotic osteochondrodysplasia 239850 Tags
Green Green List (high evidence)	AFF4	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes CHOPS syndrome 616368 Tags
Green Green List (high evidence)	ARID1A	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Coffin-Siris syndrome 2 Tags
Green Green List (high evidence)	ARID1B	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes intellectual disability coffin-siris syndrome Coffin-Siris syndrome 1 Tags
Green Green List (high evidence)	PHF6	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 Expert list Expert Review Green Phenotypes intellectual disability dysmorphism Coffin-Siris-like disorder Tags
Green Green List (high evidence)	SMARCA2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Tags
Green Green List (high evidence)	SMARCA4	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Coffin-Siris syndrome 4 Coffin-Siris Syndrome Tags
Green Green List (high evidence)	SMARCB1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Coffin-Siris syndrome 3 Coffin-Siris Syndrome Tags
Green Green List (high evidence)	SMARCE1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Coffin-Siris syndrome 5 Tags
Green Green List (high evidence)	SOX11	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes coffin-siris syndrome Tags
Red Red List (low evidence)	AIP	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red UKGTN Phenotypes Acromegaly Growth hormone secreting pituitary adenoma Tags
Red Red List (low evidence)	ARSB	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes Mucopolysaccharidosis type VI (Maroteaux-Lamy) arylsulfatase B deficiency Tags
Red Red List (low evidence)	CDKN1C	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)	Sources Expert Review Red UKGTN Tags
Red Red List (low evidence)	CTSA	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources UKGTN Phenotypes Galactosialidosis Tags
Red Red List (low evidence)	D2HGDH	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes D-2-hydroxyglutaric aciduria Tags
Red Red List (low evidence)	EXT2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Seizures, scoliosis and macrocephaly syndrome, 616682 Tags
Red Red List (low evidence)	FBXO31	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Autosomal recessive mental retardation 45, 615979 Tags
Red Red List (low evidence)	GALNS	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources UKGTN Phenotypes Mucopolysachharidosis IVA (Morquio) Tags
Red Red List (low evidence)	GNE	2 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Sialuria Tags
Red Red List (low evidence)	GNPTAB	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources UKGTN Phenotypes Mucolipidosis II alpha/beta, mucolipidosis III alpha/beta Tags
Red Red List (low evidence)	HPGD	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Primary hypertrophic osteoarthropathy autosomal recessive 1, 259100 Tags
Red Red List (low evidence)	INSR	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red UKGTN Phenotypes Rabson-Mendenhall syndrome 262190, Donohue syndrome 246200 Tags
Red Red List (low evidence)	LAMTOR2	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Tags
Red Red List (low evidence)	LTBP4	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Autosomal recessive cutis laxa, Type 1C Tags
Red Red List (low evidence)	MAGEL2	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes Schaaf Yang Tags
Red Red List (low evidence)	MMP14	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Winchester syndrome 27790 Tags
Red Red List (low evidence)	MMP2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Tags
Red Red List (low evidence)	NOTCH2	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources UKGTN Phenotypes Hajdu Cheney Tags
Red Red List (low evidence)	RBMX	2 reviews 1 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Red Literature Phenotypes Shashi X-linke mental retardation Tags
Red Red List (low evidence)	RET	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red UKGTN Phenotypes Multiple endocrine neoplasia IIB Tags
Red Red List (low evidence)	RIN2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes MACS syndrome Tags
Red Red List (low evidence)	SH3PXD2B	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Frank-Ter Haar syndrome 249420 Tags
Red Red List (low evidence)	SLCO2A1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Hypertrophic osteoarthropathy Tags
Red Red List (low evidence)	SNX14	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Tags
Red Red List (low evidence)	STAT3	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red UKGTN Phenotypes Job Hyper IgE recurrent infection Tags
Red Red List (low evidence)	TBC1D24	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Red Tags
Red Red List (low evidence)	THRA	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red UKGTN Phenotypes Congenital hypothyroidism Tags
Red Red List (low evidence)	WDR81	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red UKGTN Phenotypes Cerebellar ataxia with mental retardation Tags

Coarse facial features including Coffin-Siris-like disorders (Version 0.58)

4 reviewers

38 Entities

38 reviewed, 10 green

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