The PRRT2 gene located at 16p11 encodes proline-rich transmembrane protein with the heterozygous PRRT2 mutation being commonly reported. The most common variant found was the c.649dup.(Arg217Profs*8). Various case reviews documenting pathogenic PRRT2 variants reported an association with paroxysmal movement disorders, including paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy, paroxysmal kinesigenic dyskinesia associated with infantile convulsions (PKD/IC), also known as infantile convulsions with choreoathetosis syndrome paroxysmal non-kinesigenic dyskinesia (PNKD), hemiplegic migraine, and exercise-induced dyskinesia. However, more recent reports have also documented mutation associated with a broader clinical picture presenting with congenital microcephaly, severe learning difficulties, and pharmacoresistant encephalopathy. We hereby report a patient who presented with paroxysmal dyskinesia, harbouring the mutation variant on PRRT2 gene. At 5 months of age, our proband presented to emergency because of jerking movements while in a moving car. This was followed by generalized tonic-clonic seizures and kinesigenic posturing. The latter would occur tens of times per day and a specific trigger did not always prevail. The movements responded well to low-dose carbamazepine and genetic studies confirmed a mutated variant of c.649dup.(Arg217Profs*8).

Paroxysmal non-kinesigenic dyskinesia (PNKD) is an autosomal dominant condition characterized by recurring dystonia or mixed chorea and ballism caused by emotional stress, exhaustion, coffee, alcohol, menstruation, and other factors. Here, we provide a large family PNKD pedigree from mainland China, where the same c.20C4T (p.Ala7Val) mutation in exon 1 of the PNKD gene was genetically confirmed to be present in nine affected individuals. Here, we report a rarely described Asian PNKD pedigree and aim to widen the clinical and genetic spectrum of PNKD while also providing fresh diagnostic insights for this rare condition.

Paroxysmal movement disorders (PxMD) are characterized by episodic involuntary movements and include paroxysmal dyskinesias (PD) and episodic ataxias (EA). Although reported in the medical literature since 1892, the exact prevalence in children is unknown. To determine the prevalence and clinical characteristics of PxMD in the pediatric population in the Republic of Ireland. Cross-sectional cohort study across pediatric neurology services in the Republic of Ireland incorporating retrospective chart, telephone and clinical reviews. Seventy-nine cases met the inclusion criteria (PD = 37, EA = 38, Alternating Hemiplegia of Childhood = 4). Point prevalence for all PxMD was 6.5 cases per 100,000 persons aged less than 18 years (PD 3/100,000, EA 3.1/100,000, Alternating Hemiplegia of Childhood 0.3/100,000). Sixty-four cases were clinically reviewed by the research team (PD = 33, EA = 31). A cause was identified in 38 % (24/64). The highest investigation yield was from single-gene testing (38 %, 9/24) followed by gene panels (25 %, 11/44). Variable evolution patterns were seen. In PD, 55 % (18/33) resolved and 30 % (10/33) improved. This was due to medication in 61 % (20/33), trigger avoidance in 6 % (2/33) and spontaneous remission in 18 % (6/33). In EA, 45 % (14/31) resolved and 42 % (13/31) improved, with spontaneous remission or improvement in 48 % (17/33). This study adds to the PxMD knowledge base by determining PxMD prevalence in a pediatric population for the first time. This prevalence is higher than previous adult population estimates. An aetiology was identified in one-third. A large proportion can expect symptom improvement either with medications, trigger avoidance or spontaneous remission over time.

ATX-FGF/SCA27A has been exclusively associated with heterozygous variants in the FGF14 gene, presenting with postural tremor, slowly progressive cerebellar ataxia, and psychiatric and behavioral disturbances. This study describes the first case of ATX-FGF/SCA27A linked to a biallelic frameshift variant in the FGF14 gene. Whole-exome sequencing (WES) was conducted using the Illumina NovaSeq 6000 platform, and the identified variant was confirmed using Sanger sequencing. We report the first case of autosomal recessive FGF14-related cerebellar ataxia caused by a c.75del variant resulting in p.Leu26Serfs*51 truncation of the FGF14 protein. This variant was found in a patient born to consanguineous parents and presented with a complex congenital nonprogressive cerebellar disorder accompanied by neurodevelopmental delay, intellectual disability, and prominent drug-responsive paroxysmal non-kinesigenic dyskinesia. Segregation analysis confirmed that the homozygous variant was inherited from heterozygous parents who developed mild gait ataxia and tremor in their 40s. Biallelic loss-of-function variants in FGF14 are a rare cause of inherited cerebellar ataxia and expand the current genetic spectrum of ATX-FGF14. © 2024 International Parkinson and Movement Disorder Society.