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.
The neurological phenotypes associated with GNAO1 mutations appear to lie on a spectrum, and it is possible that the c.607G>A (p.Gly203Arg) variant characterizes a phenotype with both severe epilepsy and chorea.
Given the side effects and complications associated with neuroleptics and deep brain stimulation, respectively, topiramate is recommended for the first-line management of severe chorea associated with a GNAO1 mutation.
The SCA17 clinical phenotype includes characteristics associated with cerebellar and cortical atrophy such as ataxia, dementia, epilepsy, chorea and parkinsonian features.
We screened a cohort of 181 patients with features of primary progressive ataxia and chorea for spinocerebellar ataxias 17 (SCA17) mutation after excluding other known SCAs, Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and non-genetic causes.
A deleterious homozygous four-nucleotide deletion causing frameshift deletion in PANK2 gene (c.1426_1429delATGA, p.M476 fs) was identified in an 8 years old girl with dystonia, bone fracture, muscle rigidity, abnormal movement, lack of coordination and chorea.
Children with deletions or intragenic mutations of FOXG1 also have postnatal microcephaly, morphologic abnormalities of the corpus callosum, and choreiform movements.
In continuation with this observation, we analyzed a small cohort of 39 patients with HD phenocopy syndrome and detected the C9orf72 expansion in one female patient (2.6%) with two-year lasting mild generalized chorea and severe oro-bucco-lingual dyskinesia, who complained on forgetfullness (neuropsychological testing revealed dysexecutive syndrome with preserved episodic memory and recognition), unexplainable fears and increased appetite.
We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine.
This is the first report of chorea in patients confirmed to have the FA genetic abnormality and broadens further the clinical phenotype associated with the FA genotype.