Clinical manifestations included faciobrachial dystonic seizures (FBDS) in 11 of 35 (31.4%) patients, all with LGI1 antibodies; a combination of gait instability, brainstem dysfunction, and sleep disorder associated with IgLON5 antibodies in 10 (28.6%); acute confusion, memory loss, and behavioral changes suggesting autoimmune encephalitis (AE) in 9 (25.7%; 2 patients with AMPAR, 2 with NMDAR, 2 with GABAbR, 2 with LGI1, and 1 with CASPR2 antibodies); and rapidly progressive cognitive deterioration in 5 (14.3%; 3 patients with IgLON5 antibodies, 1 with chorea; 1 with DPPX antibody-associated cerebellar ataxia and arm rigidity; and 1 with CASPR2 antibodies).
The mutually exclusive appearance of lightning-like myoclonic jerks triggered by action in SGCE mutation carriers and of continuous chorea of all limbs in TITF-1 mutation carriers phenotypically discriminated both genetic disorders.
We identified a homozygous mutation affecting the GAF-B domain of the 3',5'-cyclic nucleotide phosphodiesterase PDE2A gene (c.1439A>G; p.Asp480Gly) as the candidate novel genetic cause of chorea in the proband.
These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome.
Considering that chorea in this patient might be due to the disruption of a gene at either of the 4p15.32 or 4q33 breakpoints, CLCN3 was considered as a candidate gene.
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.
Stepwise regression analysis revealed no effect of DRD3Ser9Gly on chorea, dystonia, or motor fluctuations in PD, despite incorporating established clinical risk factors to avoid overlooking an effect of genotype.
The family presented here broadens the clinical spectrum of parkinsonism to include tics and chorea, in addition to the parkinsonian-pyramidal phenotype, in connection with FBXO7 mutations and points to an intrafamilial phenotypic variation.
Distinct but milder phenotypes with choreiform movements in siblings with compound heterozygous mutations in the transcription preinitiation mediator complex subunit 17 (MED17).
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.