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Early onset or syndromic epilepsy

Region: ISCA-37423-Gain

8p23.1 recurrent region (includes GATA4) Gain

Green List (high evidence)
Chromosome: 8
GRCh38 Position: 8242542-11908820
Haploinsufficiency Score:
Triplosensitivity Score: Emerging evidence suggesting dosage sensitivity is associated with clinical phenotype
Required percent of overlap: 60%
Variant types: CNV Gain

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Following Genomics England clinical review and NHS Genomic Medicine Service approval, the genomic coordinates and triplosensitivity score (from 3 to 2) of this region were updated based on ClinGen Region Curation Results (version on 05 Aug 2022). Regardless of the change in triplosensitivity score, it was deemed appropriate for this regions to remain green as evidence to support pathogenicity remains.
Created: 2 Feb 2023, 3:13 p.m. | Last Modified: 2 Feb 2023, 3:13 p.m.
Panel Version: 3.31
Only two cases with epilepsy have been reported to date. Following consultation with Clinical team, decided to maintain Green rating as CNVs with variable penetrance are reported in clinical practice and can be relevant diagnostically; however, adding watchlist tag to monitor for clear evidence of particularly reduced penetrance at which stage the rating may be reviewed.
Created: 4 Oct 2022, 11:28 a.m. | Last Modified: 4 Oct 2022, 11:28 a.m.
Panel Version: 2.595
The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
Created: 16 Mar 2022, 1:39 p.m. | Last Modified: 16 Mar 2022, 1:39 p.m.
Panel Version: 2.500

Publications

Created: 16 Mar 2022, 1:39 p.m.
Last Modified: 16 Mar 2022, 1:39 p.m.
Panel version: 3.31

Rebecca Foulger (Genomics England curator)

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested rating: Green. Evidence for inclusion: PMID:28533195.
Created: 15 Aug 2019, 2:42 p.m. | Last Modified: 15 Aug 2019, 2:42 p.m.
Panel Version: 1.239

Publications

Created: 15 Aug 2019, 2:42 p.m.
Last Modified: 15 Aug 2019, 2:42 p.m.
Panel version: 1.239

Details

ISCA ID
ISCA-37423-Gain
ISCA Region Name
8p23.1 recurrent region (includes GATA4) Gain
Chromosome
8
GRCh38 Coordinates
8242542-11908820
Haploinsufficiency Score
Triplosensitivity Score
Emerging evidence suggesting dosage sensitivity is associated with clinical phenotype
Required percent of overlap
60%
Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • Expert Review Green
  • ClinGen
Phenotypes
  • Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele.
  • mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (incl. prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (e.g., atrioventricular septal defect). Other reported features include macrocephaly, behavioral abnormalities (e.g., attention deficit disorder), seizures, hypotonia and ocular and digital anomalies (poly/syndactyly)
  • congenital heart disease
  • 8p23.1 duplication syndrome
Tags
watchlist
Clinvar variants
Variants in
Penetrance
None
Variant types
CNV Gain
Publications

History Filter Activity

2 Feb 2023, Gel status: 3

Changed GRCh38, Changed Triplosensitivity Score

Arina Puzriakova (Genomics England Curator)

GRCh38 position for ISCA-37423-Gain was changed from 8261773-11908210 to 8242542-11908820. Triplosensitivity Score for ISCA-37423-Gain was changed from 3 to 2.

4 Oct 2022, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to Region: ISCA-37423-Gain.

16 Mar 2022, Gel status: 3

Changed Haploinsufficiency Score, Changed Required Overlap Percentage

Arina Puzriakova (Genomics England Curator)

Haploinsufficiency Score for ISCA-37423-Gain was changed from None to . Required Overlap Percentage for ISCA-37423-Gain was changed from 80 to 60.

15 Aug 2019, Gel status: 3

Changed Haploinsufficiency Score, Added New Source

Rebecca Foulger (Genomics England curator)

Haploinsufficiency Score for ISCA-37423-Gain was changed from to None. Source NHS GMS was added to Region: ISCA-37423-Gain.

11 Dec 2018, Gel status: 4

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

11th December 2018 After extensive review and curation the Genetic epilepsy sydrome panel is ready to be promoted to Version 1.

7 Sep 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Louise Daugherty (Genomics England Curator)

Region: ISCA-37423-Gain was added Region: ISCA-37423-Gain was added to Genetic Epilepsy Syndromes. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37423-Gain was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for Region: ISCA-37423-Gain were set to 21933911; 23345203 Phenotypes for Region: ISCA-37423-Gain were set to Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele.; mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (incl. prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (e.g., atrioventricular septal defect). Other reported features include macrocephaly, behavioral abnormalities (e.g., attention deficit disorder), seizures, hypotonia and ocular and digital anomalies (poly/syndactyly); congenital heart disease; 8p23.1 duplication syndrome