Early onset or syndromic epilepsy
Gene: CASK
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
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
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.
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
Source Wessex and West Midlands GLH was added to CASK.
Source NHS GMS was added to CASK.
Zornitza Stark: Seizures reported in around 20
Gene: cask has been classified as Green List (High Evidence).
Gene: cask has been classified as Green List (High Evidence).
Publications for gene: CASK were set to
Mode of inheritance for gene: CASK 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)
Phenotypes for gene: CASK were changed from to Mental retardation and microcephaly with pontine and cerebellar hypoplasia 300749; Mental retardation, with or without nystagmus 300422
Expert Review Amber was added to CASK. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to CASK. Panel: Genetic Epilepsy Syndromes
CASK was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert
CASK was created by Sarah Leigh