Browsing by Subject "Developmental disabilities"
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Item A 2-Year-Old Child with Alazami Syndrome with Newly Reported Findings of Immune Deficiency, Periventricular Nodular Heterotopia, and Stroke; Broadening the Phenotype of Alazami(Sage, 2023-07-27) Fauntleroy-Love, Kristin D.; Wilson, Theodore E.; Padem, Nurcicek; Golomb, Meredith R.; Pediatrics, School of MedicineAlazami syndrome is a rare autosomal recessive neurodevelopmental disorder due to loss-of-function variants in the La ribonucleoprotein 7 (LARP7) gene. Children with Alazami syndrome are most often affected by a combination of primordial dwarfism, intellectual disability, and distinctive facial features. Previous cases have been primarily found in consanguineous families from the Middle East, Asia, and North Africa. We present a 21-month-old Caucasian male from the Midwest United States with nonconsanguineous parents who presented with frequently reported findings of unusual facial features, poor growth, cardiac and genitourinary findings, and developmental delay; less-frequently reported findings, including transient erythroblastopenia of childhood (TEC) and immune deficiency; and never-before reported findings of periventricular nodular heterotopia and stroke. He developed stroke during a hospitalization for Hemophilus influenzae meningitis. The possible contributions of LARP7 to TEC, immune deficiency, brain malformation, and stroke are discussed. Guidelines for the care of Alazami patients are proposed.Item Art Therapy Interventions for Individuals with Down Syndrome(2015) Tsai, Mu-Chien; King, JulietThis study was an integrative literature review exploring the research published on art therapy interventions with individuals with Down syndrome. In order to expand the collected resources, secondary sources and expanded search terms. such as developmental disabilities and intellectual disability, were used for gathering more data to support this study. Three important outcomes were categorized: Intellectual and communicative difficulties are present; 2) Developmental and behavioral art therapy approaches and haptic art materials are particularly suitable for working with developmentally impaired people; 3) Facilitating personal expression, improving social skills, enhancing self-esteem, and fostering cognitive development are four therapeutic goals for this population. Based on these outcomes and the analyses of the collected data, an art therapy treatment plan for people diagnosed with Down syndrome was generated. The limitations and recommendations were also discussed.Item Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements(Sage, 2021) Abdelmoumen, Imane; Jimenez, Sandra; Valencia, Ignacio; Melvin, Joseph; Legido, Agustin; Diaz-Diaz, Mayela M.; Griffith, Christopher; Massingham, Lauren J.; Yelton, Melissa; Rodríguez-Hernández, Janice; Schnur, Rhonda E.; Walsh, Laurence E.; Cristancho, Ana G.; Bergqvist, Christina A.; McWalter, Kirsty; Mathieson, Iain; Belbin, Gillian M.; Kenny, Eimear E.; Ortiz-Gonzalez, Xilma R.; Schneider, Michael C.; Neurology, School of MedicineObjective: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.Item Case Report: Birth Outcome and Neurodevelopment in Placental Malaria Discordant Twins(ASTMH, 2019-03) Conroy, Andrea L.; Bangirana, Paul; Muhindo, Mary K.; Kakuru, Abel; Jagannathan, Prasanna; Opoka, Robert O.; Liechty, Edward A.; Nakalembe, Miriam; Kamya, Moses R.; Dorsey, Grant; John, Chandy C.; Pediatrics, School of MedicineMaternal infection during pregnancy can have lasting effects on neurodevelopment, but the impact of malaria in pregnancy on child neurodevelopment is unknown. We present a case of a 24-year-old gravida three woman enrolled at 14 weeks 6 days of gestation in a clinical trial evaluating malaria prevention strategies in pregnancy. She had two blood samples test positive for Plasmodium falciparum using loop-mediated isothermal amplification before 20 weeks of gestation. At 31 weeks 4 days of gestation, the woman presented with preterm premature rupture of membranes, and the twins were delivered by cesarean section. Twin A was 1,920 g and Twin B was 1,320 g. Both placentas tested negative for malaria by microscopy, but the placenta of Twin B had evidence of past malaria by histology. The twins' development was assessed using the Bayley Scales of Infant and Toddler Development-Third Edition. At 1 year chronologic age, Twin B had lower scores across all domains (composite scores: cognitive, Twin A [100], Twin B [70]; motor, Twin A [88], Twin B [73]; language, Twin A [109], Twin B [86]). This effect persisted at 2 years chronologic age (composite scores: cognitive, Twin A [80], Twin B [60]; motor, Twin A [76], Twin B [67]; language, Twin A [77], Twin B [59]). Infant health was similar over the first 2 years of life. We report differences in neurodevelopmental outcomes in placental malaria-discordant dizygotic twins. Additional research is needed to evaluate the impact of placental malaria on neurodevelopmental complications.Item Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial(American Medical Association, 2017-10-24) Laptook, Abbot R.; Shankaran, Seetha; Tyson, Jon E.; Munoz, Breda; Bell, Edward F.; Goldberg, Ronald N.; Parikh, Nehal A.; Ambalavanan, Namasivayam; Pedroza, Claudia; Pappas, Athina; Das, Abhik; Chaudhary, Aasma S.; Ehrenkranz, Richard A.; Hensman, Angelita M.; Van Meurs, Krisa P.; Chalak, Lina F.; Hamrick, Shannon E. G.; Sokol, Gregory M.; Walsh, Michele C.; Poindexter, Brenda B.; Faix, Roger G.; Watterberg, Kristi L.; Frantz, Ivan D., III; Guillet, Ronnie; Devaskar, Uday; Truog, William E.; Chock, Valerie Y.; Wyckoff, Myra H.; McGowan, Elisabeth C.; Carlton, David P.; Harmon, Heidi M.; Brumbaugh, Jane E.; Cotten, C. Michael; Sánchez, Pablo J.; Hibbs, Anna Maria; Higgins, Rosemary D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of MedicineImportance: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions: Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results: Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance: Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.Item Emergency Department Utilization Among Pediatric and Young Adults with Intellectual and Developmental Disabilities (2009-2014)(2019-04) Mullen, Cody J.; Stone, Cynthia; Menachemi, Nir; Monahan, Patrick; Johnston, AnnIntroduction: The prevalence of those aged 3-25 with an intellectual and developmental disability (I/DD), has increased 17.1% from 1997 to 2008. This study focused on these I/DD: autism spectrum disorder (ASD), cerebral palsy, learning disabilities and spina bifida. Previous studies have found that individuals with an I/DD use health services and the emergency department (ED) more frequently, regardless of payer. Methods: This dissertation will describe and define the characteristics of ED use among children and young adults with an I/DD. A repeated, cross-section of annual data of a national sample distributed by the Agency for Healthcare Research and Quality Healthcare Utilization Project National Emergency Department Sample will be analyzed from 2009-2014. This approach will document the primary clinical reason for ED use, the appropriateness of the need for a visit, and demographic, geographic, and temporal correlates for medical, injury, and psychiatric care visits in the ED. The appropriateness of need will be assessed by the New York University (NYU) Emergency Department Diagnosis Classification method for medical care visits. A logistic regression model will be specified for each visit type. Results: The sample included 386,632 visits with an I/DD diagnosis. The NYU classification method found that 44.6% of all visits for ASD were classified as nonemergent yet the other three I/DD had a non-emergent visit rate ranging 25.9%-28.8%. The ASD sub-sample was 51.8% of all visits for psychiatric care and 50.5% of all visits for injury care. All independent variables tested: admission on weekend, ED trauma level, age, sex, payer source, patient zip code income quarterlies, and patient rurality, were found to be statistically different for each model. Conclusion: The findings indicate the need for development of interventions that are specific to reducing non-emergent ED utilization for children and young adults with a diagnosis of ASD and interventions developed for reduction of emergent ED care for the other I/DD’s. In addition, unique interventions are needed to reduce the utilization of the ED for psychiatric care specifically for the ASD population and utilization of the ED for injury care for all I/DD diagnoses.Item Macrocephaly and developmental delay caused by missense variants in RAB5C(Oxford University Press, 2023) Koop, Klaas; Yuan, Weimin; Tessadori, Federico; Rodriguez-Polanco, Wilmer R.; Grubbs, Jeremy; Zhang, Bo; Osmond, Matt; Graham, Gail; Sawyer, Sarah; Conboy, Erin; Vetrini, Francesco; Treat, Kayla; Płoski, Rafal; Pienkowski, Victor Murcia; Kłosowska, Anna; Fieg, Elizabeth; Krier, Joel; Mallebranche, Coralie; Alban, Ziegler; Aldinger, Kimberly A.; Ritter, Deborah; Macnamara, Ellen; Sullivan, Bonnie; Herriges, John; Alaimo, Joseph T.; Helbig, Catherine; Ellis, Colin A.; van Eyk, Clare; Gecz, Jozef; Farrugia, Daniel; Osei-Owusu, Ikeoluwa; Adès, Lesley; van den Boogaard, Marie-Jose; Fuchs, Sabine; Bakker, Jeroen; Duran, Karen; Dawson, Zachary D.; Lindsey, Anika; Huang, Huiyan; Baldridge, Dustin; Silverman, Gary A.; Grant, Barth D.; Raizen, David; Undiagnosed Diseases Network; van Haaften, Gijs; Pak, Stephen C.; Rehmann, Holger; Schedl, Tim; van Hasselt, Peter; Medical and Molecular Genetics, School of MedicineRab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C. All but one patient with missense variants (n = 9) exhibited macrocephaly, combined with mild-to-moderate developmental delay. Patients with loss of function variants (n = 2) had an apparently more severe clinical phenotype with refractory epilepsy and intellectual disability but a normal head circumference. Four missense variants were investigated experimentally. In vitro biochemical studies revealed that all four variants were damaging, resulting in increased nucleotide exchange rate, attenuated responsivity to guanine exchange factors and heterogeneous effects on interactions with effector proteins. Studies in C. elegans confirmed that all four variants were damaging in vivo and showed defects in endocytic pathway function. The variant heterozygotes displayed phenotypes that were not observed in null heterozygotes, with two shown to be through a dominant negative mechanism. Expression of the human RAB5C variants in zebrafish embryos resulted in defective development, further underscoring the damaging effects of the RAB5C variants. Our combined bioinformatic, in vitro and in vivo experimental studies and clinical data support the association of RAB5C missense variants with a neurodevelopmental disorder characterized by macrocephaly and mild-to-moderate developmental delay through disruption of the endocytic pathway.Item MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia(Wiley, 2021) Meng, Linyan; Isohanni, Pirjo; Shao, Yunru; Graham, Brett H.; Hickey, Scott E.; Brooks, Stephanie; Suomalainen, Anu; Joset, Pascal; Steindl, Katharina; Rauch, Anita; Hackenberg, Annette; High, Frances A.; Armstrong-Javors, Amy; Mencacci, Niccolò E.; Gonzàlez-Latapi, Paulina; Kamel, Walaa A.; Al-Hashel, Jasem Y.; Bustos, Bernabé I.; Hernandez, Alejandro V.; Krainc, Dimitri; Lubbe, Steven J.; Van Esch, Hilde; De Luca, Chiara; Ballon, Katleen; Ravelli, Claudia; Burglen, Lydie; Qebibo, Leila; Calame, Daniel G.; Mitani, Tadahiro; Marafi, Dana; Pehlivan, Davut; Saadi, Nebal W.; Sahin, Yavuz; Maroofian, Reza; Efthymiou, Stephanie; Houlden, Henry; Maqbool, Shazia; Rahman, Fatima; Gu, Shen; Posey, Jennifer E.; Lupski, James R.; Hunter, Jill V.; Wangler, Michael F.; Carroll, Christopher J.; Yang, Yaping; Medical and Molecular Genetics, School of MedicineThe Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum.Item Neurodevelopment in Young Children Born to HIV-Infected Mothers: A Meta-analysis(American Academy of Pediatrics, 2018-02) McHenry, Megan S.; McAteer, Carole I.; Oyungu, Eren; McDonald, Brenna C.; Bosma, Chris B.; Mpofu, Philani B.; Deathe, Andrew R.; Vreeman, Rachel C.; Biostatistics, School of Public HealthCONTEXT: HIV-infected (HIV+) children have worse neurodevelopmental outcomes compared with HIV-uninfected children. However, little is known regarding the differences in neurodevelopment between young HIV+ children, HIV-exposed but uninfected (HEU) children, and HIV-unexposed and uninfected (HUU) children. OBJECTIVE: To systematically review and meta-analyze data on neurodevelopmental performance between young HIV+, HEU, and HUU children. DATA SOURCES: We systematically searched the following electronic bibliographic databases: Ovid Medline, Embase, PsycINFO, Education Resources Information Center, and the Cochrane Database of Systematic Reviews. STUDY SELECTION: Studies were selected on the basis of defined inclusion criteria. Titles, abstracts, and full texts were assessed by 2 independent reviewers. DATA EXTRACTION: Data were extracted by 2 independent reviewers and cross-checked by 2 additional reviewers. RESULTS: Forty-five studies were identified for inclusion in the systematic review, and of these, 11 were included in the meta-analysis on the basis of availability of Bayley Scales of Infant and Toddler Development scores. Within the meta-analysis, when compared with their HUU peers, HIV+ and HEU children had lower cognitive and motor scores. HIV+ and HEU children with antiretroviral (ARV) exposure had lower cognitive and motor scores compared with those without ARV exposure. LIMITATIONS: We were unable to control adequately for intravenous drug use, geographic location, or quality of the assessment independently. CONCLUSIONS: Both HIV+ and HEU children had worse developmental outcomes compared with HUU children. HIV+ and HEU children with ARV exposure also had worse developmental outcomes compared with those without exposure; however, these results should be interpreted with caution. More research is needed to identify the impact of ARV exposure on young children.Item Preterm Neuroimaging and School-Age Cognitive Outcomes(American Academy of Pediatrics, 2018-07) Hintz, Susan R.; Vohr, Betty R.; Bann, Carla M.; Taylor, H. Gerry; Das, Abhik; Gustafson, Kathryn E.; Yolton, Kimberly; Watson, Victoria E.; Lowe, Jean; DeAnda, Maria Elena; Ball, M. Bethany; Finer, Neil N.; Van Meurs, Krisa P.; Shankaran, Seetha; Pappas, Athina; Barnes, Patrick D.; Bulas, Dorothy; Newman, Jamie E.; Wilson-Costello, Deanne E.; Heyne, Roy J.; Harmon, Heidi M.; Peralta-Carcelen, Myriam; Adams-Chapman, Ira; Duncan, Andrea Freeman; Fuller, Janell; Vaucher, Yvonne E.; Colaizy, Tarah T.; Winter, Sarah; McGowan, Elisabeth C.; Goldstein, Ricki F.; Higgins, Rosemary D.; Pediatrics, School of MedicineBACKGROUND AND OBJECTIVES: Children born extremely preterm are at risk for cognitive difficulties and disability. The relative prognostic value of neonatal brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear. Our objectives were to relate near-term conventional brain MRI and early and late CUS to cognitive impairment and disability at 6 to 7 years among children born extremely preterm and assess prognostic value. METHODS: A prospective study of adverse early and late CUS and near-term conventional MRI findings to predict outcomes at 6 to 7 years including a full-scale IQ (FSIQ) <70 and disability (FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated associations of neuroimaging with outcomes, adjusting for perinatal-neonatal factors. RESULTS: A total of 386 children had follow-up. In unadjusted analyses, severity of white matter abnormality and cerebellar lesions on MRI and adverse CUS findings were associated with outcomes. In full regression models, both adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0-129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1-6.7) remained associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI 3.6-111) were associated with FSIQ <70. Predictive accuracy of stepwise models was not substantially improved with the addition of neuroimaging. CONCLUSIONS: Severe but rare adverse late CUS findings were most strongly associated with cognitive impairment and disability at school age, and significant cerebellar lesions on MRI were associated with disability. Near-term conventional MRI did not substantively enhance prediction of severe early school-age outcomes.