Background: Three therapeutic strategies have radically changed the therapeutic scenario for spinal muscular atrophy (SMA). However, therapeutic response differs between individuals. There is a need to identify biomarkers to further assess therapeutic response and to better understand which variables determine the extent of response. Methods: We conducted a study using an optimized digital droplet PCR-based method for the ultra-sensitive detection of SMN transcript in serum EVs from SMA 2 individuals treated with nusinersen over 14 months. In parallel, we investigated levels of serum and CSF neurofilament heavy chain (pNF-H) in the same cohort. Results: Expression of flSMN transcript in EVs of SMA 2 individuals prior to nusinersen was lower than in controls (0.40 vs 2.79 copies/ul; p <  0.05) and increased after 14 months of nusinersen (0.40 vs 1.11 copies/ul; p <  0.05). The increase in flSMN with nusinersen was significantly higher in younger individuals (p <  0.05). Serum pNF-h was higher in non-treated individuals with SMA 2 than in controls (230.72 vs 22.88 pg/ml; p <  0.05) and decreased with nusinersen (45.72 pg/ml at 6 months, 39.02 pg/ml at 14 months). CSF pNF-h in SMA 2 individuals also decreased with nusinersen (248.04 pg/ml prior to treatment, 197.10 pg/dl at 2 months, 104.43 pg/dl at 6 months, 131.03 pg/dl at 14 months). Conclusions: We identified an increase decline of flSMN transcript in serum EVs of SMA 2 individuals treated with nusinersen that was more pronounced in the younger individuals. Our results indicate that flSMN transcript expression in serum EVs is a possible biomarker in SMA to predict or monitor the response to treatment.

The presence of more than one genetic/genomic disorder is not uncommon. It is therefore essential to continuously consider new signs and symptoms over time. Administration of gene therapy could be extremely difficult in particular situations.

BackgroundBackground: Chromosome microarray analysis (CMA) can detect copy number variants (CNV) beyond the resolution of standard G-banded karyotyping. De novo or inherited microdeletions may cause autosomal dominant movement disorders. Objectives Objectives: The purpose of this study was to analyze the clinical characteristics, associated features, and genetic information of children with deletions in known genes that cause movement disorders and to make recommendations regarding the diagnostic application of CMA. Methods Methods: Clinical cases published in English were identified in scientific databases (PubMed, ClinVar, and DECIPHER) from January 1998 to July 2019 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Cases with deletions or microdeletions greater than 300 kb were selected. Information collected included age, sex, movement disorders, associated features, and the size and location of the deletion. Duplications or microduplications were not included. ResultsResults: A total of 18.097 records were reviewed, and 171 individuals were identified. Ataxia (30.4%), stereotypies (23.9%), and dystonia (21%) were the most common movement disorders. A total of 16% of the patients demonstrated more than one movement disorder. The most common associated features were intellectual disability or developmental delay (78.9%) and facial dysmorphism (57.8%). The majority (77.7%) of microdeletions were smaller than 5 Mb. We find no correlation between movement disorders, their associated features, and the size of microdeletions. Conclusions Conclusions: Our results support the use of CMA as an investigational test in children with movement disorders. As the majority of identified articles were case reports and small case series (low quality), future efforts should focus on larger prospective studies to examine the causation of microdeletions in pediatric movement disorders.Movement disorders in children are divided into two categories: hyperkinetic and hypokinetic movements. Pediatric hyperkinetic movements (PMD) are defined and classified by the Taskforce on Childhood Movement Disorders as dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies. 1,2 Pediatric hypokinetic movements are characterized by a decrease in the number of movements and are also referred to as hypokineticrigid syndrome or parkinsonism. 3 In 2016, a new nomenclature

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