Background: Several genetic causes of paroxysmal dyskinesia have been revealed during the last
years. However, the cause of complex dyskinesia remains elusive in some patients.
A homozygous loss-of-function mutation in the 3′, 5′-cyclic nucleotide phosphodiesterase
PDE2A gene was recently reported in one patient with childhood-onset choreodystonia. The
choreodystonia was preceded by paroxysmal dyskinesia and associated with cognitive
impairment and interictal EEG abnomalities. Here, we report on three new cases (two
children siblings and one adult) with biallelic PDE2A mutations to delineate the phenotype related to this gene.
Methods: The patients’ DNA underwent trio whole-exome sequencing. A retrospective analysis
of their phenotype with video-documented movement disorder is reported.
Results: We identified in PDE2A a homozygous gain of stop codon mutation (c.1180C > T; p.(Gln394*) in the siblings
and compound heterozygous mutations in the young adult patient (missense c.419C > T;
p.[P140L] and splice-site mutation). All three patients had a cognitive impairment
or developmental delay. The phenotype of the two oldest patients, aged 9 and 28 years-old,
was characterized by childhood-onset refractory paroxysmal dyskinesia initially misdiagnosed
as epilepsy due to interictal EEG abnormalities. One of them developed chronic choreodystonia
in the disease course. The youngest patient aged 15 months showed a documented epilepsy
at the age of 4 months and no paroxysmal dyskinesia to date.
Conclusion: Together with the previously reported case, our three patients confirm that biallelic
PDE2A mutations are a cause of childhood-onset refractory paroxysmal dyskinesia with cognitive
impairment, sometimes associated with interictal baseline choreodystonia and EEG abnormalities
or epilepsy.
