Ronald L. Thibert
Harvard University
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Featured researches published by Ronald L. Thibert.
American Journal of Medical Genetics | 1996
Anna M. Larson; Julianna E. Shinnick; Elias A. Shaaya; Elizabeth A. Thiele; Ronald L. Thibert
Angelman syndrome (AS) is a neurogenetic disorder. The goal of this study was to investigate the primary health issues affecting adults with AS and to further characterize the natural history and genotype–phenotype correlations. Standardized phone interviews with caregivers for 110 adolescents and adults with AS were conducted. The impact of age, sex, and genotype on specific outcomes in neurology, orthopedics, internal medicine, and psychiatry were investigated. The mean age of individuals with AS was 24 years (range 16–50y). Active seizures were present in 41% of individuals, and 72% had sleep dysfunction. Significant constipation was present in 85%, and 32% were overweight or obese, with obesity disproportionately affecting women. Scoliosis affected 50% with a mean age at diagnosis of 12 years, and 24% of those diagnosed with scoliosis required surgery, an intervention disproportionately affecting men. Sixty‐eight percent were able to walk independently, and 13% were able to speak 5 or more words. Self‐injurious behavior was exhibited in 52% of individuals. The results of this study indicate that epilepsy severity may assume a bimodal age distribution: seizures are typically most severe in early childhood but may recur in adulthood. While late‐adolescent and adult sleep patterns were improved when compared to the degree of sleep dysfunction present during infancy and childhood, the prevalence of poor sleep in adults remained quite high. Primary areas of clinical management identified include the following: seizures, sleep, aspiration risk, GERD, constipation, dental care, vision, obesity, scoliosis, bone density, mobility, communication, behavior, and anxiety.
Pediatric Neurology | 2013
Ronald L. Thibert; Anna M. Larson; David T. Hsieh; Annabel R. Raby; Elizabeth A. Thiele
Angelman syndrome is a neurogenetic disorder characterized by the loss or reduction of the ubiquitin-protein ligase E3A enzyme. Angelman syndrome results from a deletion or mutation of the maternally inherited 15q11.2-13.1 region, paternal uniparental disomy of chromosome 15, or an imprinting error. Epilepsy is common and may present with multiple seizure types, including nonconvulsive status epilepticus. Seizures are often intractable and typically require broad-spectrum antiepileptic medications. Dietary therapy has also proved successful in Angelman syndrome. Electroencephalographic patterns include notched δ and rhythmic θ activity and epileptiform discharges. Sleep disorders are also common, often characterized by abnormal sleep-wake cycles. Movement disorders are nearly universal in Angelman syndrome, most frequently presenting with ataxia and tremor. Neurocognitive impairment is always present to varying degrees, and expressive speech is typically severely affected. Individuals with Angelman syndrome often manifest psychiatric comorbidities including hyperactivity, anxiety, and challenging behaviors such as aggression and self-injury. We focus on a comprehensive whole-child approach to the diagnosis and long-term clinical care of individuals with Angelman syndrome.
Autism Research | 2013
Nora Urraca; Julie Cleary; Victoria Brewer; Eniko K. Pivnick; Kathryn McVicar; Ronald L. Thibert; N. Carolyn Schanen; Carmen Esmer; Dustin Lamport; Lawrence T. Reiter
Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism‐associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2‐q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum. Autism Res 2013, ●●: ●●–●●.
Epilepsia | 2009
Ronald L. Thibert; Kerry D. Conant; Eileen K. Braun; Patricia Bruno; Rana R. Said; Mark P. Nespeca; Elizabeth A. Thiele
Purpose: Angelman syndrome (AS) commonly presents with epilepsy (>80%). The goal of this study was to examine the natural history and various treatments of epilepsy in AS in a large population.
Developmental Medicine & Child Neurology | 2013
Agnies M. van Eeghen; Margaret B. Pulsifer; Vanessa L. Merker; Ann M. Neumeyer; Elmer E. van Eeghen; Ronald L. Thibert; Andrew J. Cole; Fawn Leigh; Scott R. Plotkin; Elizabeth A. Thiele
Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy.
Epilepsia | 2015
Tiziana Pisano; Adam L. Numis; Sinéad Heavin; Sarah Weckhuysen; Marco Angriman; Arvid Suls; Barbara Podesta; Ronald L. Thibert; Kevin Shapiro; Renzo Guerrini; Ingrid E. Scheffer; Carla Marini; Maria Roberta Cilio
To describe the antiepileptic drug (AED) treatment of patients with early infantile epileptic encephalopathy due to KCNQ2 mutations during the neonatal phase and the first year of life.
Epilepsia | 2009
Kerry D. Conant; Ronald L. Thibert; Elizabeth A. Thiele
Sleep disturbances and epilepsy are common in Angelman syndrome (AS). This study examines seizure variables and sleep in a large AS cohort. Sleep disturbances and epilepsy were assessed in 290 individuals with AS using two questionnaires, including the Behavioral Evaluation of Disorders of Sleep (BEDS). Sensitivity to the sleeping environment, decreased nightly hours of sleep, and a difficulty initiating sleep were significantly correlated with the presence of epilepsy, particularly focal seizures. Use of multiple anticonvulsant drugs was shown to affect sleep. No significant associations were present between molecular subtypes of AS and individual sleep factors. Sleep problems appeared to be associated with epilepsy in individuals with AS, especially with focal and absence seizures and multiple seizure types. Results were consistent with those of prior studies assessing sleep in AS. Severity of epilepsy and use of anticonvulsant drugs may be related to a higher degree of sleep disturbance in this population.
American Journal of Medical Genetics Part A | 2014
Wen-Hann Tan; Lynne M. Bird; Ronald L. Thibert; Charles A. Williams
Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS‐like syndrome that is clinically and molecularly distinct from AS. These AS‐like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single‐gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan–McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single‐gene disorders include Pitt–Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat–Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single‐gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work‐up of individuals with AS‐like syndromes.
Epilepsia | 2012
Anna M. Larson; Robin C.C. Ryther; Melanie Jennesson; Alexandra L. Geffrey; Patricia Bruno; Christina J. Anagnos; Ali H. Shoeb; Ronald L. Thibert; Elizabeth A. Thiele
Purpose: Disrupted sleep patterns in children with epilepsy and their parents are commonly described clinically. A number of studies have shown increased frequency of sleep disorders among pediatric epilepsy patients; however, few have characterized the association between epilepsy and parental sleep quality and household sleeping arrangements. The purpose of this study was to explore the effect of pediatric epilepsy on child sleep, parental sleep and fatigue, and parent‐child sleeping arrangements, including room sharing and cosleeping.
Epilepsia | 2014
Kerry D. Conant; Brenda M Finucane; Nicole Cleary; Ashley Martin; Candace Muss; Mary Delany; Erin Murphy; Olivia T. Rabe; Kadi Luchsinger; Sarah J. Spence; Carolyn Schanen; Orrin Devinsky; Edwin H. Cook; Janine M. LaSalle; Lawrence T. Reiter; Ronald L. Thibert
Seizures are common in individuals with duplications of chromosome 15q11.2‐q13 (Dup15q). The goal of this study was to examine the phenotypes and treatments of seizures in Dup15q in a large population.