Early onset or syndromic epilepsy

Gene: NDE1

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: 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)

16p13.11 deletion and NDE1 mutations. AR lissencephaly 4 with microcephaly. Bakircioglu et al, 2011 - 6 offspring from 3 consang families - 2 Pakistani and 1 Turkish. Seizures began by 3 months and evolved into complex partial and tonic-clonic seizures. 2 diff truncting mutations identified. Alkuraya et al, 2011 - 2 unrelated consang families from Saudi - first family - no seizures, 2nd family the boy developed seizures - not sure about sister. 2 truncating mutations identified. Tan et al, 2017 - table 1 - comparing phenotypes in all reported cases 7/9 families reported with seizures.

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
?Microhydranencephaly, 605013; Lissencephaly 4 (with microcephaly), 614019

Publications

• 22523559
• 30637988

Comment on list classification: Promoted from amber to green. NDE1 is confirmed to be a causative gene of Lissencephaly by OMIM and Gene2Phenotype. Both sources list seizures as a phenotype of the disease. There are 3 papers (PMID:21529752, 21529751, 22526350) reporting on 5 unrelated families with 8 affected individuals who have Lissencephaly and have different variants in the NDE1 gene. All patients are of Pakistani, Turkish or Saudi Arabian descent.

Created: 26 Nov 2018, 5:07 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this brain development disorder.

Created: 17 Aug 2018, 9:15 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Lissencephaly 4 (with microcephaly), MIM#614019

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