Constance Smith‐Hicks
A5013213289- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Family and Disability Support Research
- Child Nutrition and Feeding Issues
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Chromatin Remodeling and Cancer
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- RNA modifications and cancer
- Cellular transport and secretion
- Congenital heart defects research
- Behavioral and Psychological Studies
- Child Development and Digital Technology
- Neuroendocrine Tumor Research Advances
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Cerebrovascular and genetic disorders
- Down syndrome and intellectual disability research
- Obsessive-Compulsive Spectrum Disorders
- Attention Deficit Hyperactivity Disorder
Kennedy Krieger Institute
2016-2025
Johns Hopkins University
2013-2024
Johns Hopkins Medicine
2011-2024
University of Tübingen
2023
Lurie Children's Hospital
2023
Ashland (United States)
2021
Washington Center
2018
University of Washington
2018
University College London
2018
Marche Polytechnic University
2018
<h3>Objective</h3> To characterize the neurologic phenotypes associated with <i>COL4A1/2</i> mutations and to seek genotype–phenotype correlation. <h3>Methods</h3> We analyzed clinical, EEG, neuroimaging data of 44 new 55 previously reported patients <i>COL4A1/COL4A2</i> mutations. <h3>Results</h3> Childhood-onset focal seizures, frequently complicated by status epilepticus resistance antiepileptic drugs, was most common phenotype. EEG typically showed epileptiform discharges in context...
SATB2‐associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted case reports small series without in‐depth phenotypic characterization or genotype‐phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals a molecularly confirmed diagnosis...
Abstract An increasing number of individuals with intellectual developmental disorder (IDD) and heterozygous variants in BCL11A are identified, yet our knowledge manifestations mutational spectrum is lacking. To address this, we performed detailed analysis 42 -related IDD (BCL11A-IDD, a.k.a. Dias-Logan syndrome) ascertained through an international collaborative network, reviewed 35 additional previously reported patients. Analysis 77 affected identified 60 unique disease-causing (30...
Neurodevelopmental disorders are frequently associated with sleep disturbances. One class of neurodevelopmental disorders, the genetic synaptopathies, is caused by mutations in genes encoding proteins found at synapse. Mutations these cause derangement synapse development and function. We utilized a validated instrument, Children’s Sleep Habits Questionnaire (CSHQ) to examine nature abnormalities occurring individuals two synaptopathies—Phelan–McDermid syndrome (PMD) (N = 47, male 23, female...
Abstract The objective of this study was to investigate the effectiveness levetiracetam for treatment tics in children with Tourette syndrome (TS). Levetiracetam, an atypical anticonvulsant, has been suggested open‐label protocols be effective tic‐suppressing agent individuals TS. A double blind, randomized, placebo‐controlled, cross‐over trial performed medication moderate moderately‐severe tics. Subjects received, a randomized sequence, 4‐weeks (maximum dose 30 mg/kg/day) or placebo,...
To determine safety and perform a preliminary assessment of dose-dependent efficacy dextromethorphan in normalizing electrographic spikes, clinical seizures, behavioral cognitive functions girls with Rett syndrome.We used prospective randomized, open-label trial fast metabolizers to examine the effect on core features syndrome. Interictal spike activity seizures were determined using EEG parent reporting. Cognitive data obtained Mullen Scales Early Learning Vineland Adaptive Behavior Scales,...
The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling cases. Here, we describe seven individuals who have diverse yet overlapping anomalies, and all de novo missense FBXW11 identified whole exome or genome not reported the gnomAD database. Their phenotypes include striking neurodevelopmental, digital, jaw, eye one individual, features resembling Noonan syndrome, a...
Neurodevelopmental disorders (NDD) caused by protein phosphatase 2A (PP2A) dysfunction have mainly been associated with de novo variants in PPP2R5D and PPP2CA, more rarely PPP2R1A. Here, we aimed to better understand the latter characterizing 30 individuals often recurrent this PP2A scaffolding Aα subunit.Most cases were identified through routine clinical diagnostics. Variants biochemically characterized for activity interaction other subunits.We describe 16 different PPP2R1A, 21 of whom...
Plain Language SummaryWhat is this summary about?Rett syndrome a rare condition that affects how the brain develops and functions. Gastrointestinal problems are experienced by nearly everyone with Rett (most often constipation). The medication trofinetide (DAYBUE™) was studied in clinical trials, where it showed benefit reducing some of neurologic symptoms syndrome. most common side effects trials were diarrhea vomiting; aspiration rarely seen. To help caregivers healthcare providers support...
Abstract Genetic variants in chromatin regulators are frequently found neurodevelopmental disorders, but their effect disease etiology is rarely determined. Here, we uncover and functionally define pathogenic the modifier EZH1 as cause of dominant recessive disorders 19 individuals. encodes one two alternative histone H3 lysine 27 methyltransferases PRC2 complex. Unlike other subunits, which involved cancers developmental syndromes, implication human development largely unknown. Using...
Abstract Monogenic disorders account for a large proportion of population-attributable risk neurodevelopmental disabilities. However, the data necessary to infer causal relationship between given genetic variant and particular disorder is often lacking. Recognizing this scientific roadblock, 13 Intellectual Developmental Disabilities Research Centers (IDDRCs) formed consortium create Brain Gene Registry (BGR), repository pairing clinical with phenotypic from participants variants in putative...
To examine neurobehavioral findings in three genetic syndromes (PTEN hamartoma tumor syndrome, Malan syndrome [mutations the NFIX gene], and SYNGAP1-related disorder), a mixed group of other neurodevelopmental (NDGS), idiopathic disorder, neurotypical control participants.
Rett syndrome (RTT) is caused by MECP2 mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) also reported and a speculated cause of sudden death RTT. The purpose this study was to correlate QTc RTT patients with age, clinical severity, genotype. 100 (98 females, 2 males) mutations underwent baseline evaluation (KKI-RTT Severity Scale) measurement (standard 12 lead electrocardiogram) as part our prospective natural history study. Mean the cohort 422.6...