Early onset or syndromic epilepsy

Gene: TBCD

Green List (high evidence)

AR early onset encephalopathy with brain atrophy and thin corpus callosum - Miyake et al 2016 - 8 children from 4 unrelated families - 6 of these from 3 families all had seizures. Flex et al 2016 - 7 children from 5 unrelated families - 5 individuals had epileptic seizures. Edvardson et al 2016 - 4 patients from 2 unrelated families - all had 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
Encephalopathy progressive early-onset with brain atrophy and thin corpus callosum, 617193

Publications

• 28158450
• 27666370

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 Early-Onset Neurodegenerative Encephalopathy, which can present with seizures. Sufficient cases of seizures (>3) in PMID:27666370 and PMID:27666374 for inclusion on panel.

Created: 12 Nov 2018, 2:43 p.m.

In 8 children from 4 unrelated families, Miyake et al (PMID:27666374) identified homozygous or compound het variants in TBCD. Seizures were reported in 3 families (Table 2) and were reported as GTS (Chinese family 3), GTS/GTCS (Israel family 4) and West syndrome/cataplexy (Japanese Family 2).

Created: 12 Nov 2018, 2:41 p.m.

Flex et al 2016 (PMID:27666370) report that biallelic variants in TBCD cause a disease with neurodevelopmental and neurodegenerative features including early-onset encephalopathy and seizures (amongst other symptoms). Their study included 7 subjects from 5 unrelated families. Epileptic seizures were reported in 5 individuals (including one case of incidental seizures) from 4 families, including two siblings (F118_346 and F118_347). In two additional siblings from family 2 carrying the same compound heterozygous variants in TBCD, the brother had seizures, and the sister did not.

Created: 12 Nov 2018, 2:40 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this progressive neurological disorder.

Created: 22 Aug 2018, 5:20 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum, MIM#617193

Publications

• 27666370
• 27666374

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