1.
A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype.
Yan, L, Shen, R, Cao, Z, Han, C, Zhang, Y, Liu, Y, Yang, X, Xie, M, Li, H
BioMed research international. 2021;:6661860
Abstract
PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the PPP2R5D gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the PPP2R5D gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of PPP2R5D associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.
2.
Effects of aerobic, resistance and balance training in adults with intellectual disabilities.
Oviedo, GR, Guerra-Balic, M, Baynard, T, Javierre, C
Research in developmental disabilities. 2014;(11):2624-34
Abstract
Adults with intellectual disability (ID) have decreased cardiovascular fitness and strength present with lower rates of physical activity (PA), and often have balance and functional impairments. The purpose of this study was to investigate the effect of a combined PA program (CPAP) utilizing aerobic, strength and balance training on cardiovascular fitness, strength, balance and functional measures in a controlled clinical trial. Adults with mild to moderate ID were assigned into either the intervention group (IG; n=37) or the control group (CG; n=29). The IG trained 3 day/week, 1 h/day over 14 weeks, while the CG did not participate in any exercise program. Cardiovascular fitness, strength, balance, flexibility and functional ability were assessed pre-post training. The IG increased cardiovascular fitness (26.8 vs. 29.3 ml kg(-1) min(-1)), handgrip strength (19.2 vs. 21.9 kg), leg strength, and balance following the training period (p<.05). Body weight (70.1 vs. 68.1 kg) and body mass index (27.4 vs. 26.6 kg m(-2)) decreased (p<.05) in the IG group. The CG showed no changes in any parameter. These data suggest a combined aerobic, strength and balance exercise training program is beneficial among individuals with ID.
3.
Rufinamide as an adjuvant treatment in children with Lennox-Gastaut syndrome.
Kim, SH, Eun, SH, Kang, HC, Kwon, EJ, Byeon, JH, Lee, YM, Lee, JS, Eun, BL, Kim, HD
Seizure. 2012;(4):288-91
Abstract
PURPOSE To evaluate the efficacy of rufinamide as an add-on treatment in children and adolescents with Lennox-Gastaut syndrome (LGS). METHODS The study was an open-label, observational clinical trial of rufinamide as an add-on treatment in intractable LGS patients. This intent-to-treat trial included 4 weeks of scheduled titrated doses and a 12-week maintenance phase with a target dose of 20-40 mg/kg rufinamide, adjusted according to its effectiveness and tolerability after a baseline period of 4 weeks. The primary outcome was measured by the seizure-reduction rate according to individual seizure type over the 12-week maintenance period. RESULTS One hundred and twenty-eight patients with LGS who were determined to be unresponsive to one or more antiepileptic drugs or dietary therapy were enrolled. Of the 128 patients enrolled, 112 (87.5%) completed the study. After add-on rufinamide treatment, 46 patients (35.9%) achieved a more than 50% reduction in seizure frequency and 10 (7.8%) patients became seizure-free. When we identified those who responded with an at least 50% reduction in seizure frequency, 39.4% of the responders reported reductions in convulsive seizures, 36.4% in drop attacks, 33.3% in myoclonic seizures, and 20.0% in epileptic spasms. Overall, 32.8% of patients reported adverse effects, which were mostly mild and transient in nature. The most common adverse effects were fatigue (15 patients, 11.7%) and poor appetite (9 patients, 7.0%). Twenty-one (16.4%) patients experienced an increased seizure frequency. CONCLUSIONS Rufinamide appears to be a safe and effective adjuvant treatment for many cases of intractable LGS.