Early onset or syndromic epilepsy

Gene: SURF1

Green List (high evidence)

The frequency of seizures appears to be slightly higher than the national average. AR Leigh syndrome and AR CMT type 4K. Seizures are a feature of Leigh synodrome, however from the information on OMIM regarding patients with SURF1 mutations - seizures don't seem to be listed. On panel app they say that seizures are a common feature of Leighs but not necessarily Leighs due to SURF1 variant.

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
Charcot-Marie-Tooth disease type 4K, 616684; Leigh syndrome, due to COX IV deficiency, 256000

Publications

• 24027061
• 23829769
• 29481804

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

Comment on list classification: Updated rating from Amber to Green. Green review. Confirmed DD-G2P gene for Leigh syndrome and Complex IV deficiency, which can present with seizures. Seizures are a recognised phenotype for Leigh syndrome, although not necessarily in LS patients caused by SURF1 variants (PMID:24462369). However, in their multi-centre study, PMID:24462369 report sufficient cases of SURF1-deficient patients with seizures (6 of 44) for inclusion on this panel.

Created: 12 Nov 2018, 4:42 p.m.

PMID:28273704 found SURF1 variants in 10 Leigh syndrome patients, making it the most common variation in this study. The most common primary symptoms of patients include seizures. The article is in Chinese so the full article can not be curated at this time.

Created: 12 Nov 2018, 4:38 p.m.

Wedatilake et al. 2013 (PMID:23829769) conducted a study of 44 SURF1-deficient patients from 37 pedigrees from 10 different UK centres and two Australian centres. Seizures were found in 14% of patients (6 patients).

Created: 12 Nov 2018, 4:37 p.m.

Comment on publications: PMID:24462369 studied 8 complex IV-deficient LS individuals with PET100 variants. The authors state that they differed from individuals with SURF1 mutations in having seizures as a prominent feature (i.e. seizures aren't a prominent feature of individuals with SURF1 variants).

Created: 12 Nov 2018, 4:37 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 22 Aug 2018, 5:14 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leigh syndrome, due to COX IV deficiency, MIM#256000

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