Early onset or syndromic epilepsy

Gene: HEPACAM

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

Comment on mode of inheritance: Kept Mode of Inheritance as BIALLELIC based on post-Webex review from Helen Lord, and original comment from Zornitza Stark that AD form is not associated with seizures.

Created: 7 Sep 2019, 10:51 a.m. | Last Modified: 7 Sep 2019, 10:51 a.m.

Panel Version: 1.277

Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

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

Green List (high evidence)

AD and AR Megalencephalic leukoencephalopathy with subcortical cysts type 2B (MLPC2B) and 2A (MLC2A) respectively.The AD form MLC2B - not assoc with seizures. AR MLC2A - neurodegenerative disorder characterised by infantile onset macrocephaly and later onset of motor deterioration with ataxia and spasticity, seizures and cognitive decline of variable severity. Lopes Hernandez et al, 2011 - 10 patients from 8 families with MLC2A - all had onset of macrocephaly in the first year of life 8/10 developed seizures - all had hom/compound het variants.

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
Megalencephalic leukoencephalopathy with subcortical cysts 2A, 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, 613926

Publications

• 21419380

Comment on list classification: Promoted from amber to green based on evidence in the literature. One study (PMID: 21419380) reported 8 families with 10 patients with either homozygous or compound heterozygous variants (all different) in HEPACAM have epilepsy. Another study (PMID: 27389245) reported an Egyptian patient with a homozygous variant in this gene having generalized tonic-clonic seizure.
Megalencephalic leukoencephalopathy with subcortical cysts 2A confirmed to be associated with this gene on OMIM but not Gene2Phenotype.

Created: 15 Nov 2018, 10:28 a.m.

Green List (high evidence)

Seizures are part of this leukodystrophy disorder. Please note heterozygous variants cause an AD form, which is milder, and does not appear to be associated with seizures.

Created: 15 Aug 2018, 1:02 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM#613925

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