Early onset or syndromic epilepsy

Gene: TREX1

Green List (high evidence)

AD & AR Aicardi-Goutieres syndrome - genetically heterogeneous encephalopathy. The most severe neonatal form is typically due to TREX1 gene mutation. Seizures have been noted as a feature of this disease in individuals with TREX1 variants.

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
Aicardi-Goutieres syndrome 1 dominant and recessive, 225750; Chilblain lupus, 610448; Vasculopathy retinal with cerebral leukodystrophy, 192315

Publications

• 20876473

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

Comment on list classification: Updated rating from Amber to Green: Confirmed DD-G2P gene for Aicardi-Goutières syndrome, which can present with seizures. Seizures also reported for SLE and RVCL patients (PMID:18583934). Sufficient (>3) cases of patients with seizures from PMID:29239743 and PMID:17846997 for inclusion on panel.

Created: 8 Nov 2018, 8:54 a.m.

Comment on phenotypes: PMID:18583934 (Kavanagh et al 2008) include seizures in the clinical phenotype of Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL), Systemic Lupus Erythematosus (SLE) and Aicardi-Goutières Syndrome (AGS) (Table 2).

Created: 8 Nov 2018, 8:52 a.m.

Rice et al 2007 (PMID:17846997) collected clinical data for 123 individuals from 94 families with variants in TREX1, RNASEH2A, RNASEH2B, or RNASEH2C. Five individuals with TREX1 biallelic variants who presented at birth experienced neonatal seizures (Table 2).

Created: 5 Nov 2018, 10:57 a.m.

PMID:29239743 reviewed the records of 24 unrelated patients with Aicardi-Goutières syndrome from 6 tertiary hospitals in different Arab countries. The most common presenting signs were developmental delay and seizures. 1 patient (patient 23) had a biallelic variant in TREX1 (c.341G>A) and presented with seizures. The patient presented in utero.

Created: 3 Nov 2018, 11:44 a.m.

Comment on mode of inheritance: AR and AD mode of inheritance supported by OMIM: Retinal Vasculopathy with Cerebral Leukodystrophy (RVCL) has Autosomal Dominant inheritance. AGS has Autosomal Recessive or Autosomal Dominant inheritance for TREX1.

Created: 3 Nov 2018, 11:37 a.m.

Green List (high evidence)

Seizures are part of the phenotype.

Created: 22 Aug 2018, 6:47 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Aicardi-Goutieres syndrome 1, dominant and recessive, MIM#225750

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