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Objective: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, movement disorders, and epilepsy. Even though epilepsy is present in 50% of the individuals, it has not been investigated in detail. We describe here the phenotypic spectrum of epilepsy and associated comorbidities in patients with DLG4-related synaptopathy., Methods: We included 35 individuals with a DLG4 variant and epilepsy as part of a multicenter study. The DLG4 variants were detected by the referring laboratories. The degree of ID, hypotonia, developmental delay, and motor disturbances were evaluated by the referring clinician. Data on awake and sleep electroencephalography (EEG) and/or video-polygraphy and brain magnetic resonance imaging were collected. Antiseizure medication response was retrospectively assessed by the referring clinician., Results: A large variety of seizure types was reported, although focal seizures were the most common. Encephalopathy related to status epilepticus during slow-wave sleep (ESES)/developmental epileptic encephalopathy with spike-wave activation during sleep (DEE-SWAS) was diagnosed in >25% of the individuals. All but one individual presented with neurodevelopmental delay. Regression in verbal and/or motor domains was observed in all individuals who suffered from ESES/DEE-SWAS, as well as some who did not. We could not identify a clear genotype-phenotype relationship even between individuals with the same DLG4 variants., Significance: Our study shows that a subgroup of individuals with DLG4-related synaptopathy have DEE, and approximately one fourth of them have ESES/DEE-SWAS. Our study confirms DEE as part of the DLG4-related phenotypic spectrum. Occurrence of ESES/DEE-SWAS in DLG4-related synaptopathy requires proper investigation with sleep EEG., (© 2023 International League Against Epilepsy.)

Objective: Retention is essential in follow-up studies to reduce missing data, which can cause bias and limit the generalizability of the results. We investigated whether pre-notification letters would increase the response rates of approval forms and questionnaires and reduce the need for post-notifications in a prospective follow-up study of 17-year-old adolescents., Study Design: and settings This long-term follow-up study included 269 adolescents were randomized (1:1) into a pre-notification group (n = 132) and a no pre-notification group (n = 137). The pre-notification letter was sent prior to the approval form and questionnaires. The outcome measures were the response rates to the approval forms and questionnaires and the rate of post-notifications required., Results: The adolescents who received the pre-notifications were more likely to return approval forms (n = 88/132, 67%) than the adolescents who did not receive the pre-notifications (n = 79/137, 58%) (OR 1.5, 95% CI 0.9-2.4). The rates of returned questionnaires were higher in the pre-notification group (n = 82/88, 93%) than in the no pre-notification group (n = 68/79, 86%) (OR 2.2, 95% CI 0.8-6.3). The adolescents who did not receive the pre-notifications were more likely to need the post-notifications than the adolescents who received the pre-notifications (OR 3.0, 95% CI 1.4 to 6.5)., Conclusions: Pre-notifications decreased the need for post-notifications and may increase retention in 17-year-old adolescents. Based on our findings, pre-notification letters are recommended in future follow-up studies in adolescents., Trial Registration: The Ethics Review Committee of the Hospital District of South-West Finland approved the 17-year PIPARI Study protocol in January 2018 (23.1.2018; 2/180/2012). The study has been registered to the SWAT repository as SWAT 179. Filetoupload,1457904,en.pdf (qub.ac.uk)., (© 2023. The Author(s).)

Background: Very preterm birth may affect motor performance and social competence up to adulthood. Our objective was to describe perceived loneliness and social competence in children born very preterm in relation to motor impairment. Methods: 165 children born very preterm (birth weight ≤ 1500 g and/or gestational age < 32 weeks) were assessed at 11 years of age. Cerebral palsy (CP) was diagnosed by 2 years of age. At 11 years of age, motor outcome was assessed using the Movement Assessment Battery for Children—Second edition (Movement ABC-2). Loneliness was evaluated by using the Peer Network and Dyadic Loneliness scale and social competence by using the Multisource Assessment of Children’s Social Competence Scale. Results: In total, 6 (4%) children had CP, 18 (11%) had Developmental Coordination Disorder (DCD) (Movement ABC-2 ≤ 5th percentiles), and 141 (85%) had typical motor development. There was no correlation between percentiles for total scores of the Movement ABC-2 and perceived loneliness or social competence when the children with motor impairment (CP or DCD) were excluded. Children with DCD reported less perceived loneliness, but more problems with social competence compared to children with CP. Conclusions: It is important to recognize children born very preterm with DCD to provide interventions and support services to prevent social exclusion.