Early onset or syndromic epilepsy
Gene: PTEN
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
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
? 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 cancerCreated: 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
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.
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
Tag for-review was removed from gene: PTEN.
Source Expert Review Green was added to PTEN. Rating Changed from Red List (low evidence) to Green List (high evidence)
Tag mosaicism was removed from gene: PTEN. Tag somatic was removed from gene: PTEN. Tag for-review tag was added to gene: PTEN.
Gene: pten has been classified as Red List (Low Evidence).
Gene: pten has been classified as Red List (Low Evidence).
Tag mosaicism tag was added to gene: PTEN. Tag somatic tag was added to gene: PTEN.
Source Wessex and West Midlands GLH was added to PTEN.
Source NHS GMS was added to PTEN.
Zornitza Stark: Seizures are part of the pheno
Phenotypes for gene: PTEN were changed from to Cowden syndrome 1 158350; Lhermitte-Duclos syndrome; BANNAYAN-RILEY-RUVALCABA SYNDROME
Gene: pten has been classified as Green List (High Evidence).
Mode of inheritance for gene: PTEN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTEN were set to
Gene: pten has been classified as Green List (High Evidence).
Expert Review Amber was added to PTEN. Panel: Genetic Epilepsy Syndromes
PTEN was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PTEN was created by Sarah Leigh