Browsing by Subject "Down Syndrome"
Now showing 1 - 9 of 9
Results Per Page
Sort Options
Item Open Access Auditory-Perceptual Speech Features in Children With Down Syndrome.(American journal on intellectual and developmental disabilities, 2019-07) Jones, Harrison N; Crisp, Kelly D; Kuchibhatla, Maragatha; Mahler, Leslie; Risoli, Thomas; Jones, Carlee W; Kishnani, PriyaSpeech disorders occur commonly in individuals with Down syndrome (DS), although data regarding the auditory-perceptual speech features are limited. This descriptive study assessed 47 perceptual speech features during connected speech samples in 26 children with DS. The most severely affected speech features were: naturalness, imprecise consonants, hyponasality, speech rate, inappropriate silences, irregular vowels, prolonged intervals, overall loudness level, pitch level, aberrant oropharyngeal resonance, hoarse voice, reduced stress, and prolonged phonemes. These findings suggest that speech disorders in DS are due to distributed impairments involving voice, speech sound production, fluency, resonance, and prosody. These data contribute to the development of a profile of impairments in speakers with DS to guide future research and inform clinical assessment and treatment.Item Open Access Challenges in measuring the effects of pharmacological interventions on cognitive and adaptive functioning in individuals with Down syndrome: A systematic review.(American journal of medical genetics. Part A, 2017-11) Keeling, Lori A; Spiridigliozzi, Gail A; Hart, Sarah J; Baker, Jane A; Jones, Harrison N; Kishnani, Priya SWe systematically reviewed the measures used in pharmaceutical trials in children/adults with Down syndrome without dementia. Our purpose was to identify developmentally appropriate outcome measures capable of detecting changes in cognitive and adaptive functioning in this population. Eleven studies were included and used diverse outcome measures across the domains of language, memory, attention, behavior, and executive/adaptive functioning. Our results highlight the challenges in selecting measures capable of capturing improvements in pharmaceutical trials in individuals with DS. We offer suggestions to enhance future research, including: conducting studies with larger samples of participants with a range of developmental abilities; modifying existing/developing novel outcome measures; incorporating advances from related areas and DS observational studies; and considering alternative analytic techniques to characterize treatment effects.Item Open Access Intensive treatment of dysarthria in two adults with Down syndrome.(Developmental neurorehabilitation, 2012-01) Mahler, Leslie A; Jones, Harrison NObjective
This study investigated the impact of an established behavioural dysarthria treatment on acoustic and perceptual measures of speech in two adults with Down syndrome (DS) and dysarthria to obtain preliminary measures of treatment effect, effect size and treatment feasibility.Methods
A single-subject A-B-A experimental design was used to measure the effects of the Lee Silverman Voice treatment (LSVT®) on speech in two adults with DS and dysarthria. Dependent measures included vocal sound pressure level (dB SPL), phonatory stability and listener intelligibility scores.Results
Statistically significant improvements (p < 0.05) in vocal dB SPL and phonatory stability were present following treatment in both participants. Speech intelligibility scores improved in one of the two participants.Conclusions
These data suggest that people with DS and dysarthria can respond positively to intensive speech treatment such as LSVT. Further investigations are needed to develop speech treatments specific to DS.Item Open Access Involvement of the HERV-derived cell-fusion inhibitor, suppressyn, in the fusion defects characteristic of the trisomy 21 placenta.(Scientific reports, 2022-06) Sugimoto, Jun; Schust, Danny J; Yamazaki, Tomomi; Kudo, YoshikiSuppressyn (SUPYN) is the first host-cell encoded mammalian protein shown to inhibit cell-cell fusion. Its expression is restricted to the placenta, where it negatively regulates syncytia formation in villi. Since its chromosomal localization overlaps with the Down syndrome critical region and the TS21 placenta is characterized by delayed maturation of cytotrophoblast cells and reduced syncytialization, we hypothesized a potential link between changes in SUPYN expression and morphologic abnormalities in the TS21 placenta. Here we demonstrate that an increase in chromosomal copy number in the TS21 placenta is associated with: (1) reduced fusion of cytotrophoblast cells into syncytiotrophoblast in vivo, (2) increased SUPYN transcription, translation and secretion in vivo, (3) increased SUPYN/syncytin-1 receptor degradation in vivo, (4) increased SUPYN transcription and secretion ex vivo, (5) decreased cytotrophoblast cell fusion ex vivo, and (6) reciprocal response of changes in SUPYN and CGB in TS21 placental cells ex vivo. These data suggest direct links between immature placentation in Down syndrome and increased SUPYN. Finally, we report a significant increase in secreted SUPYN concentration in maternal serum in women with pregnancies affected by Down syndrome, suggesting that SUPYN may be useful as an alternate or additional diagnostic marker for this disease.Item Open Access Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome.(Pediatric blood & cancer, 2014-06) Hitzler, Johann K; He, Wensheng; Doyle, John; Cairo, Mitchell; Camitta, Bruce M; Chan, Ka Wah; Diaz Perez, Miguel A; Fraser, Christopher; Gross, Thomas G; Horan, John T; Kennedy-Nasser, Alana A; Kitko, Carrie; Kurtzberg, Joanne; Lehmann, Leslie; O'Brien, Tracey; Pulsipher, Michael A; Smith, Franklin O; Zhang, Mei-Jie; Eapen, Mary; Carpenter, Paul A; CIBMTR Pediatric Cancer Working CommitteeWe report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL.Item Open Access Outcome of transplantation for acute myelogenous leukemia in children with Down syndrome.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2013-06) Hitzler, Johann K; He, Wensheng; Doyle, John; Cairo, Mitchell; Camitta, Bruce M; Chan, Ka Wah; Diaz Perez, Miguel A; Fraser, Christopher; Gross, Thomas G; Horan, John T; Kennedy-Nasser, Alana A; Kitko, Carrie; Kurtzberg, Joanne; Lehmann, Leslie; O'Brien, Tracey; Pulsipher, Michael A; Smith, Franklin O; Zhang, Mei-Jie; Eapen, Mary; Carpenter, Paul A; CIBMTR Pediatric Cancer Working CommitteeData on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P < .001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P = .04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML. Overall mortality risk (HR, 2.86; P < .001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks.Item Open Access Resource Needs, Availability and Use Amongst Children with Down Syndrome and their Caregivers in Galle, Sri Lanka(2018) Logan, DilaniBackground: Down Syndrome (DS) is the most commonly identified aneuploidy amongst children in Sri Lanka, with a prevalence of 76.3%. This study intended to determine the level of disability of children with DS aged 5-12, level of caregiver burden and impacts of family access to external services and social supports in Galle, Sri Lanka. Methods: A cross-sectional survey and interview study was conducted to determine caregiver burden, the level of disability for children with DS, and their access to social supports and external services. Within the study, 125 caregivers took the Caregiver Priorities and Child Health Index of Life with Disabilities (CP-CHILD) and Caregiver Difficulties Scale (CDS) assessments and 15 participated in interviews. Simple bivariate and multivariable regression were used to determine the impacts of resource usage on the child’s level of disability and caregivers burden. Results: The mean level of disability of children with DS was 64.8 and caregiver burden was 50.2. Positively associated predictors of the level of disability include school, type, caregiver gender and income level. Approximately one-third (36.8%) of caregivers reported receiving assistance from external supports, 20% received government assistance, and 92.8% of caregivers relied on assistance from friends and family. Conclusions: Assistance from external sources and behavior therapy was shown to negatively moderate the relationship between the level of disability of the child and caregiver burden. Future longitudinal research, alongside more resource promotion and creation could improve resource access, disability levels and caregiver burden.
Item Open Access Safety and efficacy of rivastigmine in adolescents with Down syndrome: long-term follow-up.(J Child Adolesc Psychopharmacol, 2010-12) Heller, James H; Spiridigliozzi, Gail A; Crissman, Blythe G; McKillop, Jane Anne; Yamamoto, Haru; Kishnani, Priya SFollowing the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects.Item Open Access Sleep Disorders in Childhood Neurogenetic Disorders(Children, 2017-09-12) Dosier, Laura; Vaughn, Bradley; Fan, ZhengGenetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as "rare disease," but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.