Early onset or syndromic epilepsy
Gene: CDKL5
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 EIEE2. Many reported cases on OMIM: Weaving et al, 2004 - 2 aff twin girls and twin brother had a delT variant. Aff girls of a second family had a different variant. Tao et al, 2004 - 2 unrelated girls - 2 different mutations in CDKL5. Elia et al, 2008 - 3/8 unrelated Italian boys had 3 diff mutations. In2 of the boys it wasn't present in the mothers, no DNA for third mum. Nemos et al, 2009 - screened 177 early onset seizure patients. 11 girls had de novo mutation including a large deletion found by MLPA. All of the mutations were associated with random X inactivation and cell lines that exclusively expressed mutant missense mutants found they are properly localised to the nucleus.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
Epileptic encephalopathy, early infantile, 2,300672
Publications
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
Angelman syndrome-like; Epileptic encephalopathy, early infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
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
Angelman syndrome-like; Epileptic encephalopathy, early infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
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
Angelman syndrome-like; Epileptic encephalopathy, early infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
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
Angelman syndrome-like; Epileptic encephalopathy, early infantile, 2
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Allelic requirement in gene2phenotype is x-linked dominant (monoallelic in females).Created: 17 Dec 2015, 2:53 p.m.
Source Wessex and West Midlands GLH was added to CDKL5.
Source NHS GMS was added to CDKL5.
Ellen McDonagh: Comment on mode of inheritance
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to CDKL5. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to CDKL5. Panel: Genetic Epilepsy Syndromes
CDKL5 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert,Radboud University Medical Center, Nijmegen,UKGTN
CDKL5 was created by Sarah Leigh