Early onset or syndromic epilepsy

Gene: CDKL5

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 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

• 15492925
• 17993579

Green List (high evidence)

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

• Kishino et al (1995) Nature Genet 15: 70-73
• Tao et al (2004) Am J Hum Genet 75: 1149-1154

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

Green List (high evidence)

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

• Kishino et al (1995) Nature Genet 15: 70-73
• Tao et al (2004) Am J Hum Genet 75: 1149-1154

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

Green List (high evidence)

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

• Kishino et al (1995) Nature Genet 15: 70-73
• Tao et al (2004) Am J Hum Genet 75: 1149-1154

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

Green List (high evidence)

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

• Kishino et al (1995) Nature Genet 15: 70-73
• Tao et al (2004) Am J Hum Genet 75: 1149-1154

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.