Early onset or syndromic epilepsy
Gene: DNM1L
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
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.
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
Source Wessex and West Midlands GLH was added to DNM1L.
Source NHS GMS was added to DNM1L.
Zornitza Stark: Seizures/epileptic encephalopa
Mode of inheritance for gene: DNM1L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: dnm1l has been classified as Green List (High Evidence).
Gene: dnm1l has been classified as Green List (High Evidence).
Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388 to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388; refractory epilepsy; refractory focal status epilepticus
Publications for gene: DNM1L were set to 26604000
Publications for gene: DNM1L were set to
Mode of inheritance for gene: DNM1L was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388
Expert Review Amber was added to DNM1L. Panel: Genetic Epilepsy Syndromes
DNM1L was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
DNM1L was created by Sarah Leigh