Early onset or syndromic epilepsy
Gene: TANGO2
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
AR recurrent metabolic encephalomyopathic crisis with rhabdomyolosis, cardiac arrhythmias and neurodegeneration. Lalani et al, 2016 - 12 aff individuals from 9 families with episodic rhabdomyolosis - 9/12 had seizures. Hom/compound het variants detected in all, recurrent hom missense variant detected in 4 unrelated Hispanic probands and a hom deletion was found in 4 probands from 2 families of European origin. Kremer et al, 2016 - 3 unrelated individuals with recurrent encephalomyopathic crisis, epilepsy was part of the overall disease course - hom or compound het variants detected in all.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
Metabolic encephalomyopathic crises recurrent with rhabdomyolysis cardiac arrhythmias and neurodegeneration, 616878
Publications
Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least three variants reported 7 unrelated cases in which seizures are a phenotypic feature.Created: 11 Dec 2018, 10:58 a.m.
Comment on list classification: Based on reviewer's comments and sufficient evidence from the literature.Created: 11 Dec 2018, 10:51 a.m.
Biallelic pathogenic variants in TANGO2 cause Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM 616878
PMIDs: 29369572 and 30245509 are both reviews on the disorder. Epilepsy is a feature in 70-80% of the patients (29 individuals reviewed in the second article).
According to PMID: 29369572 "Seizures are observed outside the periods of crises in more than 75% of individuals". PMID 30245509 notes that seizures occurred in a small minority of patients only during periods of crises secondary to hypoglycemia or associated with arrhythmia.
TANGO2 is included in gene panels for epilepsy offered by (few) diagnostic laboratories. The gene is already present in the ID and mitochondrial disorders panels as green.
As a result, this gene can also be considered for inclusion in this panel as green.
Sources: LiteratureCreated: 10 Dec 2018, 2:27 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM 616878
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to TANGO2.
Source NHS GMS was added to TANGO2.
Konstantinos Varvagiannis: Biallelic pathogenic variants
Publications for gene: TANGO2 were set to 29369572; 30245509
Gene: tango2 has been classified as Green List (High Evidence).
Gene: tango2 has been classified as Green List (High Evidence).
Phenotypes for gene: TANGO2 were changed from Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM 616878 to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878
gene: TANGO2 was added gene: TANGO2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TANGO2 were set to 29369572; 30245509 Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration, MIM 616878 Penetrance for gene: TANGO2 were set to Complete Review for gene: TANGO2 was set to GREEN gene: TANGO2 was marked as current diagnostic