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Myoclonus classically presents as a brief (10–50 ms duration), non‐rhythmic jerk movement. The etiology could vary considerably ranging from self‐limited to chronic or even progressive disorders, the latter falling into encephalopathic pictures that need a prompt diagnosis. Beyond the etiological classification, others evaluate myoclonus' body distribution (i.e., clinical classification) or the location of the generator (i.e., neurophysiological classification); particularly, knowing the anatomical source of myoclonus gives inputs on the observable clinical patterns, such as EMG bursts duration or EEG correlate, and guides the therapeutic choices. Among all the chronic disorders, myoclonus often presents itself as a manifestation of epilepsy. In this context, myoclonus has many facets. Myoclonus occurs as one, or the only, seizure manifestation while it can also present as a peculiar type of movement disorder; moreover, its electroclinical features within specific genetically determined epileptic syndromes have seldom been investigated. In this review, following a meeting of recognized experts, we provide an up‐to‐date overview of the neurophysiology and nosology surrounding myoclonus. Through the dedicated exploration of epileptic syndromes, coupled with pragmatic guidance, we aim to furnish clinicians and researchers alike with practical advice for heightened diagnostic management and refined treatment strategies. Plain Language Summary: In this work, we described myoclonus, a movement characterized by brief, shock‐like jerks. Myoclonus could be present in different diseases and its correct diagnosis helps treatment. [ABSTRACT FROM AUTHOR]

We aimed to identify caregivers' opinions on the outcome measures that matter in clinical trials in individuals with Dravet syndrome (DS). We conducted a prospective European multicenter study based on an 11 closed questions survey developed by the French reference center for rare epilepsies and DS patients' advocacy groups. Items included questions on seizures and daily life outcomes that a clinical trial on a therapy for individuals with DS should target. Statistical analyses were performed to evaluate the impact of the country of residence and of the patients' age. The survey was answered by 153 caregivers (68%: France, 28%: Germany, and 24%: Italy) off individuals with DS. Individuals with DS included 86 males (mean age of 11.4 [interquartile: 7‐20.4] years). Families ranked as important almost all the items proposed. However, items related to daily life had the highest rank in all three countries compared to items about seizures (P = 0.02). Increase in individuals' age was associated with a higher age at diagnosis (ρ = 0.26, P = 0.02), and a lower impact of seizure duration (ρ = −0.25, P = 0.005) and on the need of hospital referral (ρ = −0.26, P = 0.005). These data can help tailor patient‐centered outcome measures in future clinical and real‐life trials for DS. [ABSTRACT FROM AUTHOR]

NAA20 is the catalytic subunit of the NatB complex, which is responsible for N‐terminal acetylation of approximately 20% of the human proteome. Recently, pathogenic biallelic variants in NAA20 were associated with a novel neurodevelopmental disorder in five individuals with limited clinical information. We report two sisters harboring compound heterozygous variant (c.100C>T (p.Gln34Ter) and c.11T>C p.(Leu4Pro)) in the NAA20 gene, identified by exome sequencing. In vitro studies showed that the missense variant p.Leu4Pro resulted in a reduction of NAA20 catalytic activity due to weak coupling with the NatB auxiliary subunit. In addition, unpublished data of the previous families were reported, outlining the core phenotype of the NAA20‐related disorder mostly characterized by cognitive impairment, microcephaly, ataxia, brain malformations, dysmorphism and variable occurrence of cardiac defect and epilepsy. Remarkably, our two patients featured epilepsy onset in adolescence suggesting this may be a part of syndrome evolution. Functional studies are needed to better understand the complexity of NAA20 variants pathogenesis as well as of other genes linked to N‐terminal acetylation. [ABSTRACT FROM AUTHOR]

Response to antiseizure medications (ASMs) can be influenced by several gene polymorphisms, causing either lower efficacy or higher occurrence of adverse drug reactions (ADRs). We investigated the clinical utility of salivary pharmacogenomic testing on epilepsy patients. A commercialized pharmacogenomic salivary test was performed in a cohort of epileptic patients. Genetic variants on five genes (i.e., CYP1A2, CYP2C9, CYP2C19, EPHX1, and ABCB1) involved in common ASMs metabolism were selected. Twenty‐one individuals (median age [Q1–Q3]: 15 [6.5–28] years) were enrolled. Six patients harboring the homozygous *1F allele in CYP1A2 could have reduced chance of response to stiripentol due to fast metabolism. CYP2C9 had reduced activity in 10 patients (alleles *2 and *3), potentially affecting phenytoin (PHT), phenobarbital (PB), primidone, lacosamide (LCM), and valproic acid metabolism. Seven patients, carrying the *2 allele of CYP2C19, had an increased risk of ADRs with clobazam (CLB), PB, PHT, LCM, brivaracetam; while one individual with the *17 allele in heterozygosity reported a CLB fast metabolism. Six patients showed a CC polymorphism of EPHX1 associated with the impaired efficacy of carbamazepine. ABCB1 polymorphisms related to drug‐resistance (3435 CC) or drug‐sensitive phenotype (CT or TT) were found in 6 out of 7 patients. Pharmacogenomic testing on saliva proved easy and safe in clinical practice to convey information for the management of epileptic patients, especially those resistant to treatment or sensitive to severe ADRs. [ABSTRACT FROM AUTHOR]

Mutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug‐resistant in this syndrome with frequent drop attacks. In a prospective study of add‐on cannabidiol (CBD), we identified three patients with SYNGAP1 mutations: two boys and one girl. Seizure onset was at 3.5, 8, and 18 months (M), respectively, with numerous atypical absences per day associated with eyelid myoclonia (2/3 patients), upper limb myoclonic jerks (2/3 patients), and drop attacks (all patients). Seizures were resistant to at least 5 antiepileptic drugs (AEDs). After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. EEGs showed an improvement regarding background activity and interictal anomalies. The last patient showed a late response at M7 of treatment with an 80% decrease in seizure frequency. Caregiver in all three evaluated as much improved the status of their children. Treatment was well‐tolerated in all, and no major adverse events (AEs) were reported. CBD showed efficacy in patients with drug‐resistant epilepsy due to SYNGAP1 mutations. Other patients with rare genetic developmental and epileptic encephalopathies with drug‐resistant epilepsies might benefit from CBD. [ABSTRACT FROM AUTHOR]