The identification of heterozygous mutations in the PRRT2 gene in paroxysmal kinesigenic dyskinesia as well as in benign familial infantile seizures linked episodic movement disorders with epilepsy.
PRRT2 gene mutations have recently been identified as a causative gene of Paroxysmal kinesigenic dyskinesia (PKD), a rare movement disorder characterised by the occurrence of chorea, dystonia or athetosis triggered by sudden action.
Four patients had a deletion of a known movement disorder gene including paroxysmal kinesigenic dyskinesia (PRRT2; n=2), SGCE (myoclonus dystonia, n=1), and TITF1 (benign hereditary chorea, n=1).
Here we develop a mouse model carrying a human GNAO1 mutation (G203R) and determine whether the clinical features of patients with this GNAO1 mutation, which includes both epilepsy and movement disorder, would be evident in the mouse model.
<b>Expert opinion</b>: After secondary paroxysmal dyskinesias, the most common paroxysmal movement disorders are likely to be PRRT2-associated paroxysmal kinesigenic dyskinesias, which respond well to small doses of carbamazepine, and episodic ataxia type 2, which often responds to acetazolamide.
The authors report 2 cases of brothers with a severe movement disorder and hypotonia without epilepsy who have been confirmed by whole exome sequencing to have a novel mutation in GNAO1.
Here we review a mechanistic model in which loss-of-function (LOF) GNAO1 alleles cause epilepsy and gain-of-function (GOF) alleles are primarily associated with movement disorders.
The disease results from an expanded sequence of CAG repeats in the huntingtin gene and leads to a movement disorder with associated cognitive and systemic deficits.
We report the case of a 29 year old woman with a complex movement disorder syndrome due to the combination of coexisting pathological triplet repeat expansions of huntingtin and ATXN8 genes.
In order to examine the effects of CAG block lengths, we have correlated ApoE genotypes with the age of onset in 145 patients symptomatic for HD with psychiatric and somatic symptoms (depression, psychosis, dementia, choreic, and other movement disorders) harbouring only modestly expanded huntingtin alleles (41-45 CAGs).
This case demonstrates that SCN1A mutations may cause movement disorders as an atypical phenotype and the case history of this patient may expand our understanding of the clinical spectrum of SCN1A-associated epileptic encephalopathy.[Published with video sequences].