Early onset or syndromic epilepsy

Gene: CNTN2

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:59 p.m. | Last Modified: 24 Feb 2025, 5:59 p.m.

Panel Version: 7.39

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: As reviewed by Sarah Graham, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 12 Jul 2024, 3:16 p.m. | Last Modified: 12 Jul 2024, 3:16 p.m.

Panel Version: 5.24

PMID:23518707 reported a consanguineous Egyptian family in which five siblings aged 11 to 14 years had seizures and were identified with a homozygous frameshift CNTN2 variant (p.Trp168fs).

PMID:34691156 reported a 10-year old boy born of unrelated parents of Han Chinese descent, with developmental delay and onset of generalised tonic-clonic seizures at 5 years of age and identified with a homozygous frameshift CNTN2 variant (p.Thr958Thrfs).

PMID:36553572 reported a 13-year-old boy with global developmental delay and epileptic encephalopathy and was associated with a homozygous nonsense variant (p.Arg314Ter) in the CNTN2 gene.

PMID:37359369 reported a consanguineous Pakistani family in which four siblings developed various types of seizures late in the first decade of their life and had global developmental,ental delay with mild intellectual disability. They were identified with a homozygous nonsense CNTN2 variant (p.Glu567Ter)

This gene has been associated with relevant phenotypes in OMIM (MIM #615400), but not yet in Gene2Phenotype.

Created: 12 Jul 2024, 3:13 p.m. | Last Modified: 12 Jul 2024, 3:13 p.m.

Panel Version: 5.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, early-onset, 5, with or without developmental delay, OMIM:615400

Publications

• 23518707
• 34691156
• 36553572
• 37359369

Green List (high evidence)

Homozygous loss-of-function variants have been reported in several unrelated families in association with epilepsy, developmental delay and ID (OMIM #615400). ClinGen gene-disease validity: definitive.

Created: 8 Jul 2024, 3:07 p.m. | Last Modified: 8 Jul 2024, 3:07 p.m.

Panel Version: 5.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 37359369
• 34691156
• 28397838
• 36553572

I don't know

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 and Helen Lord. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

AR familial myoclonic epilepsy 5 - neurological condition characterised by onset of seizures in adolescence followed by the development of cortical myocolonic tremor later in life. Some aptients also have neuropsychiatric abnormalities. Stogmann et al, 2013 - consanf Egyptian family - 5 sibs aged 11-14 - onset of seizures - different types incl complex partial and generalised. All had a hom fs mutation. Not in controls and not in 189 patients with various epilepsy syndromes. On HGMD pro missense variats in this gene reported in assoc with hypogonadotrophic hypogonadism and a missense variant assoc with congenital heart disease.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Epilepsy, myoclonic, familial adult, 5, 615400

Publications

• 23518707