Childhood onset dystonia, chorea or related movement disorder

Gene: TBC1D24

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 4 May 2024, 6:04 p.m. | Last Modified: 4 May 2024, 6:14 p.m.

Panel Version: 4.3

Comment on list classification: There are five unrelated cases reported with dystonia as a feature of the overall phenotype. Hence, this gene can be promoted to green rating at the next major update.

Created: 9 Aug 2023, 8:48 p.m. | Last Modified: 9 Aug 2023, 8:48 p.m.

Panel Version: 3.33

Five children from a large consanguineous kindred of Turkish descent were reported with severe early-onset epileptic encephalopathy, where patients had severely impaired neurologic development and neurologic deterioration with permanent neurologic sequelae, including severe hypotonia, hemiparesis with pyramidal signs, and dystonia (PMID:21087195). A homozygous truncating variant was identified in the TBC1D24 gene in these patients (PMID:23343562).

Three individuals from a family of Italian descent were reported with a syndrome with onset in infancy and comprising rolandic epilepsy, paroxysmal exercise-induced dystonia, and writer's cramp. In addition, three unrelated sporadic patients were reported with a phenotype similar to the original rolandic epilepsy - exercise-induced dystonia (RE-EID) observed in the Italian family. All these patients were identified with compound heterozygous variants in TBC1D24 (PMID:31257402).

Autosomal recessive variants in this gene has been associated with RE-EID (MIM #608105) and DEE16 (MIM #615338) among other phenotypes in OMIM and these two syndromes include dystonia as one of the clinical manifestations.

Created: 9 Aug 2023, 8:44 p.m. | Last Modified: 9 Aug 2023, 8:44 p.m.

Panel Version: 3.30

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, rolandic, with paroxysmal exercise-induce dystonia and writer's cramp, OMIM:608105; Developmental and epileptic encephalopathy 16, OMIM:615338

Publications

• 21087195
• 23343562
• 31257402

Green List (high evidence)

Three unrelated families reported with rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp (EPRPDC), an autosomal recessive neurologic disorder characterised by onset of focal seizures in infancy and exercise-induced dystonia in childhood. Features usually include involuntary movements, including facial movements, and difficulties with fine motor skills of the hand. Seizures often respond to medication and remit with age; the dystonia tends to persist. Three unrelated families reported with this specific phenotype, though variants in this gene are associated with a range of other neurological disorders and may represent a spectrum of severity.
Sources: Expert list

Created: 10 Sep 2020, 8:37 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp, MIM# 608105

Publications

• 31257402