Early onset or syndromic epilepsy

Gene: NDUFS8

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)

AR mitochondrial complex I defic nuclear type 2. Haack et al, 2012 - 3 patients including 2 sibs with complex I defic. One of the patients had epilepsy - hom variant detected, other unrelated indivdual was compound het, functional studies done. Loeffen et al, 1998 - 5 week old - erratic seizures. In the Della Marina et al, 2013 paper - talbe of patients with reported mutations in this gene so far: 2/10 reported withe pilepsy as part of clinical phenotype.

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

Panel Version: 1.188

Comment on mode of inheritance: Promoted to Green due to evidence of a seizures/epilepsy phenotype in two unrelated cases with variants in this gene.

Created: 11 Dec 2018, 2:16 p.m.

Comment on publications: PMID: 22499348 - of three patients (2 related) reported with homozygous or compound heterozygous variants in this gene, one was reported with epilepsy with a clinical diagnosis of Leigh syndrome...this patient also had a homozygous variant in NDUFS7, however the variant in NDUFS8 was attributed to the disease as their affected sister also carried this homozygous variant. She had a clinical diagnosis of Leigh syndrome, decribed with Muscular hypotonia, lactic acidosis blood and CSF, MRI lesions basal ganglia and brainstem, hypertrophic cardiomyopathy (seizures or epilepsy were not mentioned). In the other unrelated case, a clinical diagnosis of mitochondrial encephalopathy and hypertrophic cardiomyopathy was given, with Muscular hypotonia, respiratory insufficiency as other features.

Created: 11 Dec 2018, 2:11 p.m.

Comment on publications: PMID: 9837812 - erratic seizures reported in a case who was compound heterozygous for variants in NDUFS8 "At admission, the main symptoms were mild cyanosis, severe hypercarbia, a cardiac murmur, drowsiness with absent optical and acoustical blink, eye flutter, intense hypotonia, brisk tendon reflexes with ankle clonus, and erratic seizures".

Created: 11 Dec 2018, 1:56 p.m.

Comment on publications: PMID: 15159508 - does not mention seizures in the case.

Created: 11 Dec 2018, 1:50 p.m.

Comment on list classification: Curated in OMIM for Leigh syndrome due to mitochondrial complex I deficiency and in Gene2Phenotype for MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY, which include seizures as a phenotype.

Created: 11 Dec 2018, 1:46 p.m.

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 17 Aug 2018, 10:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome due to mitochondrial complex I deficiency, MIM#256000

Publications

• 22499348
• 9837812

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