Early onset or syndromic epilepsy

Gene: CASK

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)

XLD mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) - charecterised by severe intellectual disability, microcephaly and variable degrees of pontocerebellar hypoplasia. According to OMIM seizures not a common feature. Moog et al, 2011 - 25 girls with MICPH due to het loss of CASK function - 8 had seizures. Saitsu et al, 2012, 2 unrelated Japanese males ascertained for severe early onset epileptic encephalopathy consistent with a diagnosis of Ohtahara syndrome - hemizygous LOF CASK mutations (one had de novo nonsense mutation and the other had a deletion involving exon 23 inherited from mum who was a somatic mosaic) - both presented in infancy with refractory seizures. Takanashi et al, 2012 - 15 Japanese girls and 1 boy with genetically confirmed MICPCH. 8 of the girls had seizures and the boy had epilepsy - severe. Epilepsy a feature in over 50% of cases above.

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
FG syndrome, 300422 ; Mental retardation and microcephaly with pontine and cerebellar hypoplasia, 300749; Mental retardation with or without nystagmus, 300422

Publications

• 21954287

Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in unrelated cases with seizures included in their phenotype.

Created: 13 Nov 2018, 10:20 a.m.

Green List (high evidence)

Seizures reported in around 20%.

Created: 8 Aug 2018, 3:45 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
Mental retardation, with or without nystagmus, MIM#300422; FG syndrome 4, MIM#300422

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

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)