Early onset or syndromic epilepsy
Gene: DCX
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
X-linked lissencephaly 1 (more severe pheno seen in males) and X-linked subcortical laminal heterotopia (milder pheno seen in females). Berry-Kravis and Israel 1994 - fmily: 5 male infants in 2 generations - all ff infants had intractable seizures and other features. DiMario et al, 1993 - 16 year old patient and mother both with band heterotopias and seizures. Huttenlocher et al, 1994 - family in which 6 females over 4 generations had subependymal masses of heterotopic grey matter and seizures, high rate of spontaneous abortion in family. Toyamam et al, 1998 - mother and son. Mother had intractable seizures. Poolos et al, 2002 - 2 male patients with complete subcortical band heterotopia, mild MR and seizures - like female phenotype - somatic mosaics for DCX mutations - 1 missense, 1 deletion. Chou et al, 2009 - 7 year old with LISX due to bexon 5 deletion - severe pheno including seizures. Variants reported by Gleesen et al, 1998 and 2000, Aigner et al, 2003 (4 missense 3 nonsense), Haverfield et al, 2009 (3 intragenic deletions idenitifed by MLPA) and Jamuar et al, 2014 (27 causal mutations identified, 8/27 were somatic). Somatic mosaicism is a feature.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Lissencephaly, 300067; Subcortical laminal heterotopia, 300067
Publications
Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 14 variants reported.Created: 16 Oct 2018, 2:54 p.m.
Seizures are a feature of this brain development disorder.Created: 12 Aug 2018, 6:09 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Lissencephaly, X-linked, MIM#300067 and Subcortical laminal heterotopia, X-linked, MIM#300067
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: DCX were changed from Lissencephaly, X-linked 300067; Subcortical laminal heterotopia, X-linked 300067 to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Source Wessex and West Midlands GLH was added to DCX.
Source NHS GMS was added to DCX.
Zornitza Stark: Seizures are a feature of this
Gene: dcx has been classified as Green List (High Evidence).
Phenotypes for gene: DCX were changed from to Lissencephaly, X-linked 300067; Subcortical laminal heterotopia, X-linked 300067
Mode of inheritance for gene: DCX was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Gene: dcx has been classified as Amber List (Moderate Evidence).
Expert Review Amber was added to DCX. Panel: Genetic Epilepsy Syndromes
DCX was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
DCX was created by Sarah Leigh