Genetic Epilepsy

Gene: TRAPPC12

I don't know

Update - 3 unrelated families with characteristic phenotype involving microcephaly and epilepsy (Milev et al 2017, Aslanger et al 2020). 4th case from unrelated family with novel homozygous missense variants reported with no microcephaly or clinically apparent epilepsy (Aslanger et al 2020).

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3 individuals from 2 unrelated families reported by Milev et al 2017 with similar clinical phenotype: severe disability, microcephaly, hearing loss, spasticity, and characteristic brain imaging findings including pons hypoplasia, agenesis of the corpus callosum and brain atrophy. 2 of the 3 individuals had epilepsy with the third having a history of myoclonic jerks and significant MRI-B anomalies including agenesis of the corpus callosum. Fibroblasts derived from all three individuals showed a fragmented Golgi that could be rescued by expression of wild-type TRAPPC12

Aslanger et al 2020 reports a 3rd case from an unrelated family with homozygous TRAPPC12 missense variants (reported previously by Milev et al in a patient with compound het variants) in a 2 year old M with axial hypotonia, appendicular hypertonia, severe dev delay, generalized tonic-clonic seizues and microcephaly. MRI-B showed ventriculomegaly, progressive severe cerebral atrophy, and moderate cerebellar atrophy.

Aslanger et al also report a 4th case from an unrelated family with a novel homozygous TRAPPC12 variant in a 9 year old M with severe truncal hypotonia, extreme hypertonicity, severe dev delay prominent cerebellar atrophy but no microcephaly or clinically apparent epilepsy. Paroxysmal discharges were noted on EEG. This case may reflect that the phenotype is more variable than previously anticipated particularly with biallelic missense variants however we would benefit from having more reported cases to expand the phenotype.

Created: 11 Oct 2021, 12:02 a.m. | Last Modified: 11 Oct 2021, 12:02 a.m.

Panel Version: 0.1276

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity - 617669

Publications

• 28777934
• 32369837

I don't know

Comment when marking as ready: Three unrelated families with consistent phenotype including microcephaly and seizures.

Created: 11 Oct 2021, 5:39 a.m. | Last Modified: 11 Oct 2021, 5:39 a.m.

Panel Version: 0.1286

Two unrelated families reported.

Created: 25 Jan 2020, 9:31 a.m. | Last Modified: 25 Jan 2020, 9:31 a.m.

Panel Version: 0.498

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, MIM#617669

Publications

• 28777934