机构：[1]Division of Child and Adolescent Psychiatry, University of Cape Town, 46 Sawkins Road, Rondebosch, Cape Town, 7700, South Africa. petrus.devries@uct.ac.za.[2]Research and Clinical Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russian Federation.[3]SPS Pediatrična Klinika, Ljubljana, Slovenia.[4]TSA Tuberous Sclerosis Association, Nottingham, UK.[5]Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France.[6]Tor Vergata University Hospital, Rome, Italy.[7]Karolinska University Hospital, Stockholm, Sweden.[8]Novartis Farma S.p.A, Origgio, Italy.[9]Association Sclérose Tubéreuse de Bourneville, Gradignan, France.[10]Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal.[11]Universitätsklinik für Kinder-und Jugendheilkunde, Vienna, Austria.[12]Associazione Sclerosi Tuberosa ONLUS, Milan, Italy.[13]European Tuberous Sclerosis Complex Association, In den Birken, Dattein, Germany.[14]Vivantes-Klinikum Neukölln, Berlin, Germany.[15]Department of Child Neurology, Warsaw Medical University, Warsaw, Poland.[16]Sussex Kidney Unit, Royal Sussex County Hospital, Brighton, UK.[17]The Tuberous Sclerosis Multidisciplinary Management Clinic, Sydney Children's Hospital, Randwick, NSW, Australia.[18]Hospital Universitari Vall d'Hebron, Barcelona, Spain.[19]Institute of Biomedicine, University of Leon, Leon, Spain.[20]Department of Pediatric Neurology, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France.[21]Institute of Child Health, University College London, London, UK.[22]Department of Pediatrics, Peking University People's Hospital (PKUPH), Beijing, China.[23]Tallinn Children Hospital, Tallinn, Estonia.[24]Klinikverbund Kempten-Oberallgäu gGmbH, Kempten, Germany.[25]Novartis Healthcare Pvt. Ltd, Hyderabad, India.[26]National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, 886 Urushiyama, Aoi-ku, Shizuoka, Japan.[27]Hôpital Nord, Saint Etienne, France.[28]"[29]St. Sophia"[30]Children's Hospital, Athens, Greece.[29]University Medical Center, Utrecht, The Netherlands.[30]UZ Brussel Vrije Universiteit Brussel, Brussels, Belgium.
Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations.
The study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015). The most common behavioural problems (reported in > 10% of participants) were overactivity, sleep difficulties, impulsivity, anxiety, mood swings, severe aggression, depressed mood, self-injury, and obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%), attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%), and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate, severe, and profound degrees of intellectual disability (ID) were observed in 28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in 58.6% of participants, and neuropsychological deficits (performance <5th percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity were observed in children and higher rates of anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations were observed in adults. Genotype-TAND correlations showed a higher frequency of self-injury, ASD, academic difficulties and neuropsychological deficits in TSC2. Those with no mutations identified (NMI) showed a mixed pattern of TAND manifestations. Children and those with TSC2 had significantly higher rates of intellectual disability, suggesting that age and genotype comparisons should be interpreted with caution.
These results emphasize the magnitude of TAND in TSC and the importance of evaluating for neuropsychiatric comorbidity in all children and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no mutations identified. However, the high rates of unreported or missing TAND data in this study underline the fact that, even in expert centres, TAND remains underdiagnosed and potentially undertreated.
基金：
The study was funded by Novartis Pharma AG. Novartis has contributed to
the study design, data analysis, and the decision to publish. Novartis authors
reviewed the draft for submission.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区医学
小类|3 区遗传学3 区医学：研究与实验
最新[2023]版：
大类|2 区医学
小类|2 区遗传学2 区医学：研究与实验
第一作者：
第一作者机构：[1]Division of Child and Adolescent Psychiatry, University of Cape Town, 46 Sawkins Road, Rondebosch, Cape Town, 7700, South Africa. petrus.devries@uct.ac.za.
通讯作者：
推荐引用方式(GB/T 7714)：
de Vries Petrus J,Belousova Elena,Benedik Mirjana P,et al.TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study.[J].Orphanet journal of rare diseases.2018,13(1):157.doi:10.1186/s13023-018-0901-8.
APA：
de Vries Petrus J,Belousova Elena,Benedik Mirjana P,Carter Tom,Cottin Vincent...&Jansen Anna C.(2018).TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study..Orphanet journal of rare diseases,13,(1)
MLA：
de Vries Petrus J,et al."TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study.".Orphanet journal of rare diseases 13..1(2018):157
医学