POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.

POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype-phenotype correlations in individuals with POU3F3-related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA-binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3-related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype-phenotype correlations.

Measuring Effects on Pain and Quality of Life after Abobotulinum Toxin A Injections in Children with Cerebral Palsy.

Sixty-seven percent of children with cerebral palsy (CCP) experience pain. Pain is closely interrelated to diminished quality of life. Despite this, pain is an overlooked and undertreated clinical problem. The objective of this study was to examine the analgesic effect of a single lower extremity intramuscular injection of Abobotulinum toxin A/Dysport in CCP. Twenty-five CCP with at least moderate pain (r-FLACC ≥ 4) during passive range of motion were included. Localized pain and pain in everyday living were measured by r-FLACC and the Paediatric Pain Profile (PPP), respectively. Functional improvements were evaluated by the goal attainment scale (SMART GAS). Quality of life was evaluated by either the CPCHILD or the CP-QOL. The subjects were evaluated at baseline before injection, then after 4, 12, and 28 weeks. Twenty-two subjects had a significant mean and maximum localized pain reduction (p < 0.001) at four weeks post-treatment in 96% (21/22). The reduction was maintained at 12 (19/19) and 28 weeks (12/15). Daily pain evaluated by the PPP was significantly reduced and functional SMART GAS goals were significantly achieved from 4 to 28 weeks. Quality of life improved significantly at four weeks (CPCHILD). Significant functional gains and localized and daily pain reduction were seen from 4 to 28 weeks.

[Ten practical, theory-based tips for clinical course planners]. / Ti praktiske, teoribaserede råd til planlaeggere af kliniske kurser.

A list of practical advice and examples are given based on the literature. E-learning with cliffhanger text-cases can activate prior knowledge, and selected examination skills can be trained with simulated patients. Patient video recordings can be used to train clinical reasoning skills, including pattern recognition and hypothetic-deductive approaches. Interactive approaches, for example, questioning, quizzes or buzz groups imply active involvement and participation. Quizzes and MCQ-testing can provide a formative 'check-up' on learning and point to gaps in understanding for the teachers and the participants. Spacing a course with intervening assignments can enable the transfer of skills to practice.