Early onset or syndromic epilepsy

Gene: SUCLA2

Green List (high evidence)

AR mitochondrial DNA depletion syndrome type 5. OMIM: Elpeleg et al, 2005 - 1 patient had seizures, Ostergaard et al, 2007 & Carrozzo et al, 2007 - 11 patients from the Faroe Islands - Mention 1 had seizures (hom founder mutation). Carrozo et al also reported 3 patients from S Italy with similar phenotype - no mention of seizures. JAABERI ET AL, 2013, 2 Iranian cousins - no mention of 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
Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), 612073

Publications

• 15877282
• 17301081
• 23759946

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 plus sufficient cases (>3) of seizures in MMA patients (At least 3 new patients in PMID:26475597, 2 cousins from 1 family in PMID:15877282, and 1 Faroe Island patient in PMID:17287286/17301081).

Created: 13 Nov 2018, 1:42 p.m.

PMID:26475597 (Carrozzo et al 2016) report 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings in these and 46 previously reported patients. Of the 71 patients, 50 had SUCLA2 mutations and 21 had SUCLG1 mutations. Epilepsy reported as generalized seizures, unspecified epilesy or infantile spasms was mainly reported in patients with SUCLA2 variants. Only 1 patient with the SUCLG1 variant had epilepsy (5%). At least 3 cases of epilepsy listed in new patients with SUCLA2 variants (supplementary material).

Created: 13 Nov 2018, 1:40 p.m.

Jaberi et al 2013 (PMID:23759946) identified a homozygous c.751G>A transition in SUCLA2 (D251N) in 2 Iranian cousins with MIM:612073. No sign of epilepsy was seen in Patient 1. Epilepsy was not mentioned for the cousin (Patient 2).

Created: 13 Nov 2018, 12:04 p.m.

Elpeleg et al 2005 (PMID:15877282) identified a homozgyous deletion/insertion in SUCLA2 in 2 first cousins from a consanguineous Muslim family. Both cousins had generalized seizures from age 1 and age 3.

Created: 13 Nov 2018, 12:03 p.m.

In 16 patients from the Faroe islands with MIM:612073, Ostergaard et al. (2007, PMID:17287286) and Carrozzo et al, 2007 (PMID:17301081) independently identified a homozygous founder variant in SUCLA2. Seizures were reported in only one of the Faroese patients, and this patient had infantile spasms that disappeared around age 1.5 years. Carrozzo et al, 2007 (PMID:17301081) also identified 2 additional SUCLA2 variants in Italian patients but seizures were not reported for these 2 patients.

Created: 13 Nov 2018, 12:03 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this mitochondrial disorder.

Created: 22 Aug 2018, 5:08 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), MIM#612073

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