Recent progress in scientific research has facilitated accurate genetic and neuropathological diagnosis of congenital myopathies. However, given their relatively low incidence, congenital myopathies remain unfamiliar to the majority of care providers, and the levels of patient care are extremely variable. This consensus statement aims to provide care guidelines for congenital myopathies. The International Standard of Care Committee for Congenital Myopathies worked through frequent e-mail correspondences,

Background: Mitochondrial DNA depletion syndrome is an autosomal recessive disorder characterized by decreased mitochondrial DNA copy numbers in affected tissues. It has been linked to 4 genes involved in deoxyribonucleotide triphosphate metabolism: thymidine kinase 2 (TK2), deoxyguanosine kinase (DGUOK), polymerase gamma (POLG), and SUCLA2, the gene encoding the ␤-subunit of the adenosine diphosphateforming succinyl coenzyme A synthetase ligase. Objective: To highlight the variability in the clinical spectrum of TK2-related mitochondrial DNA depletion syndrome. Design: Review of patients and the literature. Setting: Tertiary care university. Patients: Four patients with mitochondrial DNA depletion syndrome and mutations in the TK2 gene. Main Outcome Measures: Definition of clinical variability. Results: Patient 1 had evidence of lower motoneuron disease and was initially diagnosed as having spinal muscular atrophy type 3. Patient 2, who is alive and ambulatory at age 9 years, presented at age 2 years with a slowly progressive mitochondrial myopathy. Patient 3 had a more severe myopathy, with onset in infancy and death at age 6 years of respiratory failure. Patient 4 had a rapidly progressive congenital myopathy with rigid spine syndrome and he died at age 19 months. Conclusion: The clinical spectrum of TK2 mutations is not limited to severe infantile myopathy with motor regression and early death but includes spinal muscular atrophy type 3-like presentation, rigid spine syndrome, and subacute myopathy without motor regression and with longer survival.

clinicaltrials.org Identifier: NCT02432885.

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Background ADCY5‐related dyskinesia is characterized by early‐onset movement disorders. There is currently no validated treatment, but anecdotal clinical reports and biological hypotheses suggest efficacy of caffeine. Objective The aim is to obtain further insight into the efficacy and safety of caffeine in patients with ADCY5‐related dyskinesia. Methods A retrospective study was conducted worldwide in 30 patients with a proven ADCY5 mutation who had tried or were taking caffeine for dyskinesia. Disease characteristics and treatment responses were assessed through a questionnaire. Results Caffeine was overall well tolerated, even in children, and 87% of patients reported a clear improvement. Caffeine reduced the frequency and duration of paroxysmal movement disorders but also improved baseline movement disorders and some other motor and nonmotor features, with consistent quality‐of‐life improvement. Three patients reported worsening. Conclusion Our findings suggest that caffeine should be considered as a first‐line therapeutic option in ADCY5‐related dyskinesia. © 2022 International Parkinson and Movement Disorder Society

This study aims to develop a comprehensive review on the issue of poor school performance for professionals in both health and education areas. It discusses current aspects of education, learning and the main conditions involved in underachievement. It also presents updated data on key aspects of neurobiology, epidemiology, etiology, clinical presentation, comorbidities and diagnosis, early intervention and treatment of the major pathologies comprised. It is a comprehensive, non-systematic literature review on learning, school performance, learning disorders (dyslexia, dyscalculia and dysgraphia), attention deficit / hyperactivity disorder (ADHD) and developmental coordination disorder (DCD). Poor school performance is a frequent problem faced by our children, causing serious emotional, social and economic issues. An updated view of the subject facilitates clinical reasoning, accurate diagnosis and appropriate treatment.

Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early onset severe form of complicated HSP. We report two additional patients with novel de novo mutations in KIF1A hereby expanding the genetic spectrum of KIF1A-related HSP. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential MRIs, therefore linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in Patient 1 and Patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199R), respectively. Therefore our report contributes to the expanding the genotypic and phenotypic spectrum of HSP caused by mutations in KIF1A.