Early onset or syndromic epilepsy

Gene: DCX

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

Green List (high evidence)

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

• 12034802
• 19098909

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.

Green List (high evidence)

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