Early onset or syndromic epilepsy

Gene: MED17

Green List (high evidence)

Comment on list classification: There are 3 unrelated families (Jewish families with potential founder variant counted as one) where affected individuals harboured biallelic MED17 variants and presented with seizures (among other syndromic symptoms). Based on available evidence, this gene can be promoted to Green at the next update.

Created: 22 Jun 2026, 9:52 a.m. | Last Modified: 25 Jun 2026, 2:30 p.m.

Panel Version: 9.13

PMID 20950787 Kaufmann et al., 2010
Homozygous variant p.L371P was identified in 9 patients from 4 Caucasus Jewish families. Five infants from four unrelated families presented soon after birth with spasticity, epilepsy, and profound psychomotor retardation. Head circumference percentiles declined, and brain MRI disclosed marked cereberal and cerebellar atrophy with severe myelination defect.

PMID: 26004231 Hirabayashi, Saitsu, & Matsumoto, 2016
2 sibs with nystagmus and sudden opistotonic posturing from the early infancy, developmental delay and marked choreiform movements with hypotonia in the childhood. The brother had a mild postnatal microcephaly. Brain MRI of the sister showed mild delay of myelination, dilated anterior horn and mild cerebellar atrophy. WES revealed comp het MED17 mutations in both: c.1013-5A>G, p. Ser338Asnfs*15 and c.1484T>G, p.Leu495Trp (in trans).

PMID: 30345598 Agostini et al., 2018
Report of two siblings presenting with failure to thrive in early years, progressive microcephaly, moderate intellectual disability, developmental delay, ataxic gait and seizures with an identical EEG pattern, and minimal cerebellar atrophy. Both sibs were comp het for MED17: p.Glu16fs and p.Gly253Arg (confirmed in trans).

PMID: 36508181 Rafiullah et al., 2022
Consanguineous family with individuals presenting with severe ID, seizure, and progressive microcephaly. Magnetic resonance imaging (MRI) of the brain showed mild brain atrophy and myelination defect. WES detected homozygous MED17 variant NM_004268.5_c.871T>C; p.Trp291Gly - confirmed het in unaffected parents and sibs.

MED17 is associated with AR Microcephaly, postnatal progressive, with seizures and brain atrophy, MIM:613668 (OMIM accessed 22nd Jun 2026).

Created: 22 Jun 2026, 9:48 a.m. | Last Modified: 22 Jun 2026, 9:59 a.m.

Panel Version: 9.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, postnatal progressive, with seizures and brain atrophy, OMIM:613668

Publications

• 20950787
• 26004231
• 30345598
• 36508181

I don't know

Sibs in PMID:26004231 had a milder phenotype and did not have seizures. Therefore, there is still currently not enough evidence to support a gene-disease association. Recommend that this gene stays Amber until further evidence is available.

Created: 20 Sep 2021, 1:12 p.m. | Last Modified: 20 Sep 2021, 1:12 p.m.

Panel Version: 2.422

Green List (high evidence)

Another pair of sibs reported, compound het variants (frameshift and missense), seizures part of the phenotype.

Created: 24 Jan 2020, 7:38 a.m. | Last Modified: 24 Jan 2020, 7:38 a.m.

Panel Version: 2.0

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly postnatal progressive with seizures and brain atrophy, 613668

Publications

• 30345598

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

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: Alison Callaway and John Taylor. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

Appears to be a founder effect in Caucasian Jews, PMID 20950787, but relatively few other variants / other publications to date.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly postnatal progressive with seizures and brain atrophy, 613668

Publications

• 20950787

Red List (low evidence)

Gene originally listed on the Intellectual disability panel V2.42.
Associated with relevant phenotypes in OMIM and as probable Gen2Phen gene. At least 2 variants reported. Homozygous variant p.L371P was identified in 9 patients from 4 Caucasus Jewish families (indicative of a founder variant)(PMID 20950787). Variants c.1013-5A>G and c.1484T>G were reported as compound heterozygotes in two siblings of non-consanguineous parents, they displayed a milder phenotype which did not include seizures.

Created: 10 Apr 2018, 10:53 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly, postnatal progressive, with seizures and brain atrophy 613668

Publications

• 26004231
• 20950787