Early onset or syndromic epilepsy

Gene: NRXN1

Green List (high evidence)

2 cases of hom/compound het variants assoc with a sever recessive MR syndrome - patients had severe epilepsy

Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.

Panel Version: 1.261

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

I don't know

Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review by Helen Lord.

Created: 7 Sep 2019, 11:42 a.m. | Last Modified: 7 Sep 2019, 11:42 a.m.

Panel Version: 1.284

Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

Comment on mode of inheritance: PMID:30031152 (Al Shehhi et al.) report heterozygous deletions of NRXN1 with phenotypes including seizures. At least PMID:21964664 (Harrison et al.) and PMID:19896112 report a biallelic mode of inheritance.

Created: 13 Aug 2019, 12:53 p.m. | Last Modified: 13 Aug 2019, 12:53 p.m.

Panel Version: 1.203

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: Green.

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

Panel Version: 1.189

Green List (high evidence)

Moller et al 2013 - idiopathic generalised epilepsy. AR Pitt Hopkins like syndrome 2 - epilepsy a feature in 2/3 patients. Zweier et al, 2009 - compound het in an affected girl (stop mutation and a gross del). Harrison et al, 2011 - 2 sisters - severe early onset MR and severe epilepsy - compound het deletions. On HGMD Pro variants reported in this gene assocaited with autism spectrum disorder - not many mention of epilepsy. In addition most variants are gross deletions including some of the gene.

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
Pitt-Hopkins-like syndrome 2 614325; {Schizophrenia, susceptibility to, 17}, 614332

Publications

• 19896112
• 22617343

Comment when marking as ready: Associated with phenotypes in OMIM and as probable Gen2Phen gene for both Pitt-Hopkins-like syndrome 2 and autism. Numerous variants reported in mono or biallelic form in cases displaying a wide range of neurodevelopmental disorders with varied features, including seizures.

Created: 3 Sep 2018, 2:52 p.m.

Comment on phenotypes: Some cases of {Schizophrenia, susceptibility to, 17} 614332 and autism also display seizures.

Created: 3 Sep 2018, 2:49 p.m.

I don't know

Seizures are part of the phenotype of both NRXN1 deletions and of bi-allelic variants.

Created: 17 Aug 2018, 11:17 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Pitt-Hopkins-like syndrome 2, MIM#614325

Publications

• 21964664
• 19896112
• 30031152
• 23533028

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)

Publications

• Zweier et al (2009) Am J Hum Genet 85: 655_666
• Gregor et al. BMC Medical Genetics 2011, 12.106

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)

Publications

• Zweier et al (2009) Am J Hum Genet 85: 655_666
• Gregor et al. BMC Medical Genetics 2011, 12.106

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)

Publications

• Zweier et al (2009) Am J Hum Genet 85: 655_666
• Gregor et al. BMC Medical Genetics 2011, 12.106

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pitt-Hopkins-like syndrome 2 (AR); severe intellectual disability (AD)

Publications

• Zweier et al (2009) Am J Hum Genet 85: 655 666
• Gregor et al. BMC Medical Genetics 2011, 12.106

Variants in this GENE are reported as part of current diagnostic practice