Early onset or syndromic epilepsy

Gene: CLN6

I don't know

PMID:30561534. Berkovic et al., 2019 report phenotypes of patients with CLN6 pathogenic variants from 13 unrelated families (homozygous in 4 families and compound het in 9 families). The typical presentation was progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures.

Created: 28 Oct 2019, 12:16 p.m. | Last Modified: 28 Oct 2019, 12:16 p.m.

Panel Version: 1.398

PMID:31216804. Zhang et al. 2019 identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy. 1 patient had a variant in CLN6 (full English text not available).

Created: 28 Oct 2019, 11:29 a.m. | Last Modified: 28 Oct 2019, 11:29 a.m.

Panel Version: 1.394

Additional case in PMID:31029456 (Matsumoto et al., 2019) of Japanese boy with a homozygous C.794_976del variant p. (Ser265del) in CLN6. Symptoms include focal seizures.

Created: 28 Oct 2019, 11:25 a.m. | Last Modified: 28 Oct 2019, 11:25 a.m.

Panel Version: 1.394

Comment on list classification: Updated rating from Red to Amber based on Amber review by Tracy Lester and PMID:21549341 (Arsov et al., 2011) where seizures are a consistent feature across families.

Created: 22 Oct 2019, 9:50 a.m. | Last Modified: 22 Oct 2019, 9:50 a.m.

Panel Version: 1.377

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: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

Could neuronal Ceroid-Lipofuscinoses be tested through a different referral pathway? AR neuronal ceroid lipofuscinosis 6 - clinical course includes seizures. Another type is known as Kufs type (adult onset) of which there is an A and B sub-type - A is characterised by myoclonic epilepsy and B is characterised by dementia. Arsov et al, 2011 - 3 families with AR Kufs disease - hom or compound het mutations in CLN6 - mutations then found in 4 additional families with Kuffs disease - yielding a total of 9 different pathogenic mutations. All patients from the 7 families had progressive myoclonic epilepsy followed by dementia - consistent with type A.

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
Ceroid lipofuscinosis neuronal, 6, 601780; Ceroid lipofuscinosis, neuronal Kufs type adult onset, 204300

Publications

• 21549341

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)