Early onset or syndromic epilepsy

Gene: DNM1L

Green List (high evidence)

AD optic atrophy 5 and AD & AR lethal encephalopathy due to defective mitochondrial peroxisomal fission 1. Many patients develop refractory seizures. Vanstone et al 2016 - 7 year old boy unrealted Caucasian parents - epilepsy onset at 1 year - de novo het missense variant. Fahrner et al, 2016 - 2 unrelated boys - presented at ages 4 and 5 with epileptic encephalopathy - de novo het missese variant in both. In vitro functional studies done. Chao et al, 2016 - boy developed epilepsy around 5 months of age - de novo het missense variant - maternal somatic mosaicism suggested, expression studies done.

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

Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Encephalopathy lethal due to defective mitochondrial peroxisomal fission, 614388; Optic atrophy, 610708

Publications

• 26604000
• 27145208

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 mode of inheritance: Both autosomal dominant and autosomal recessive inheritance reported by OMIM for 'Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388'.

Created: 3 Dec 2018, 1:42 p.m.

Comment on list classification: Updated rating from Amber to Green: Green rating by Zornitza. At least 3 cases in the literature of unrelated patients with DNM1L variants and seizures (1 in PMID:26604000 and 2 in PMID:27145208).

Created: 22 Nov 2018, 4:27 p.m.

Fahrner et al., 2016 (PMID:27145208) report identical novel missense variants (c.1207C-T, R403C) in DNM1L in two unrelated probands who experienced normal development for several years before presenting with refractory focal status epilepticus and subsequent rapid neurological decline.

Created: 22 Nov 2018, 4:23 p.m.

Green List (high evidence)

Seizures/epileptic encephalopathy are a reported feature in some patients.

Created: 12 Aug 2018, 6:47 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, MIM#614388

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