Early onset or syndromic epilepsy

Gene: PTEN

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 5:34 p.m. | Last Modified: 3 Mar 2022, 5:34 p.m.

Panel Version: 2.491

There is enough evidence for this gene to be rated GREEN at the next major review.

Based on the green reviews below, together with Helen Brittain's comments that PTEN is associated with seizures in some and therefore on this basis, plus the other green reviews, I think it is reasonable to promote back to green. As seizures are not a prominent part of the phenotype in many.

Created: 8 Jul 2020, 8:01 a.m. | Last Modified: 8 Jul 2020, 8:01 a.m.

Panel Version: 2.113

I don't know

Added tags: 'mosaicism' and 'somatic'.

Created: 15 Aug 2019, 10:25 a.m. | Last Modified: 15 Aug 2019, 10:25 a.m.

Panel Version: 1.235

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed to demote PTEN from Green to Red. This panel is not the appropriate test for somatic variant detection due to the coverage. R110 Segmental overgrowth disorders (panel #98) should be used where megalencephaly is present to allow detection of somatic mosaic mutations.

Created: 15 Aug 2019, 10:24 a.m. | Last Modified: 30 Mar 2020, 11:32 a.m.

Panel Version: 2.25

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. Technical notes: ? Appropriate pathway for testing PTEN.

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)

? Appropriate pathway for testing PTEN. AD Cowden syndrome - characterised by macrocephaly, facial trichilemmomas and increased risk of breast, thyroid and endometrial carcinoma. Seizures have been reported as a feature. Longy et al, 1998 - family A - patient 3 had seizures. No seizures/epilepsy reported in other patients/families. Adachi et al, 2018 - 1 patient had seizures as an adult. Ghusayani et al, 2018 - 11 year old boy who develped drug-resistant focal seizures on 5th day of life, MRI revealed hemimegalencephaly. Although epilepsy is not a major feature in PTEN and problematic as risk for cancer

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

Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cowden syndrome, 158350; Lhermitte-Duclos syndrome, 158350; Macrocephaly/autism syndrome, 605309; VATER association with macrocephaly and ventriculomegaly, 276950; {Glioma susceptibility 2}, 613028; {Meningioma}, 607174;

Publications

• 11726927
• 12085208
• 11726926

Comment on list classification: 3 cases in which a variant in PTEN is reported in individuals with Bannayan-Riley-Ruvalcaba syndrome with clinical phenotype that includes seizures.

Created: 4 Dec 2018, 5:03 p.m.

PTEN is associated with Cowden syndrome 1/Lhermitte-Duclos syndrome in OMIM and COWDEN SYNDROME 1/LHERMITTE-DUCLOS DISEASE/COWDEN DISEASE/BANNAYAN-ZONANA SYNDROME in Gene2Phenotype.

Individuals with seizures are reported in PMID: 9832032 (Longy et al 1998) - a heterozygous deletion in exon 6, 1390deIG, PMID: 29033429 (Adachi et al 2018) - heterozygous deletion in exon 5 (c.486delC) and PMID:29444762 (Ghusayni et al 2018) - c.510 T>G PTEN mutation. All are reported to have Bannayan-Riley-Ruvalcaba syndrome which is an alternative name for Cowden syndrome 1 in OMIM.

Created: 4 Dec 2018, 5:02 p.m.

Green List (high evidence)

Cowden and BRRS are germline PTEN-related conditions and can present with macrocephaly/neurodevelopmental phenotype in childhood, including ID/autism and sometimes seizures as outlined in the previous reviews. The associated cancer risk makes the condition important to diagnose.

There are also somatic PTEN-related conditions such as Proteus, but these are not under consideration for this panel. One of the reviews below refers to AKT1, which is confusing.

Created: 25 Jan 2020, 1:50 a.m. | Last Modified: 25 Jan 2020, 1:50 a.m.

Panel Version: 2.0

Seizures are part of the phenotype of PTEN-related neurodevelopmental disorders.

Created: 20 Aug 2018, 1:43 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cowden syndrome 1, MIM#158350

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