{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:48:48Z","timestamp":1761767328613,"version":"3.37.3"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of Health","award":["U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090"],"award-info":[{"award-number":["U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090","U54NS092090"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23NS119666"],"award-info":[{"award-number":["K23NS119666"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurodevelop Disord"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by <jats:italic>SHANK3<\/jats:italic> haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype\u2013phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype\u2013phenotype relationships when deletion size is taken into account.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s11689-024-09541-0","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:01:57Z","timestamp":1715338917000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical, genetic, and cognitive correlates of seizure occurrences in Phelan-McDermid syndrome"],"prefix":"10.1186","volume":"16","author":[{"given":"Tess","family":"Levy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Gluckman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paige M.","family":"Siper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Halpern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Zweifach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajna","family":"Filip-Dhima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"J. Lloyd","family":"Holder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Pilar","family":"Trelles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Berry-Kravis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig M.","family":"Powell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Latha Valluripalli","family":"Soorya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Thurm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph D.","family":"Buxbaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Kolevzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the Developmental Synaptopathies Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"issue":"7","key":"9541_CR1","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1007\/s00439-014-1423-7","volume":"133","author":"SM Sarasua","year":"2014","unstructured":"Sarasua SM, Boccuto L, Sharp JL, Dwivedi A, Chen CF, Rollins JD, et al. Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. Hum Genet. 2014;133(7):847\u201359.","journal-title":"Hum Genet"},{"key":"9541_CR2","doi-asserted-by":"publisher","first-page":"652454","DOI":"10.3389\/fgene.2022.652454","volume":"13","author":"J Nevado","year":"2022","unstructured":"Nevado J, Garc\u00eda-Mi\u00f1a\u00far S, Palomares-Bralo M, Vallesp\u00edn E, Guill\u00e9n-Navarro E, Rosell J, et al. Variability in Phelan-McDermid syndrome in a cohort of 210 individuals. Front Genet. 2022;13:652454.","journal-title":"Front Genet"},{"key":"9541_CR3","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13023-015-0323-9","volume":"10","author":"LM Oberman","year":"2015","unstructured":"Oberman LM, Boccuto L, Cascio L, Sarasua S, Kaufmann WE. Autism spectrum disorder in Phelan-McDermid syndrome: initial characterization and genotype-phenotype correlations. Orphanet J Rare Dis. 2015;10:105.","journal-title":"Orphanet J Rare Dis"},{"issue":"1","key":"9541_CR4","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/2040-2392-4-18","volume":"4","author":"L Soorya","year":"2013","unstructured":"Soorya L, Kolevzon A, Zweifach J, Lim T, Dobry Y, Schwartz L, et al. Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency. Mol Autism. 2013;4(1):18.","journal-title":"Mol Autism"},{"key":"9541_CR5","doi-asserted-by":"publisher","unstructured":"Garc\u00eda-Bravo C, Mart\u00ednez-Pi\u00e9drola RM, Garc\u00eda-Bravo S, Rodr\u00edguez-P\u00e9rez MP, Mart\u00edn-G\u00f3mez AS, Fern\u00e1ndez-G\u00f3mez G, Palacios-Ce\u00f1a D. Living with and managing seizures among parents of children diagnosed with Phelan-McDermid syndrome: a qualitative study using in-depth interviews. Eur J Pediatr. 2023. https:\/\/doi.org\/10.1007\/s00431-023-05285-6.","DOI":"10.1007\/s00431-023-05285-6"},{"issue":"6","key":"9541_CR6","doi-asserted-by":"publisher","first-page":"104746","DOI":"10.1016\/j.ejmg.2023.104746","volume":"66","author":"IFM de Coo","year":"2023","unstructured":"de Coo IFM, Jesse S, Le TL, Sala C. Consensus recommendations on Epilepsy in Phelan-McDermid syndrome. Eur J Med Genet. 2023;66(6):104746.","journal-title":"Eur J Med Genet"},{"issue":"8","key":"9541_CR7","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1002\/ajmg.a.63312","volume":"191","author":"S Srivastava","year":"2023","unstructured":"Srivastava S, Sahin M, Buxbaum JD, Berry-Kravis E, Soorya LV, Thurm A, et al. Updated consensus guidelines on the management of Phelan-McDermid syndrome. Am J Med Genet A. 2023;191(8):2015\u201344.","journal-title":"Am J Med Genet A"},{"issue":"10","key":"9541_CR8","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1111\/epi.13506","volume":"57","author":"JL Holder Jr","year":"2016","unstructured":"Holder JL Jr, Quach MM. The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations. Epilepsia. 2016;57(10):1651\u20139.","journal-title":"Epilepsia"},{"issue":"9","key":"9541_CR9","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1016\/j.seizure.2014.06.008","volume":"23","author":"MG Figura","year":"2014","unstructured":"Figura MG, Coppola A, Bottitta M, Calabrese G, Grillo L, Luciano D, et al. Seizures and EEG pattern in the 22q13.3 deletion syndrome: clinical report of six Italian cases. Seizure. 2014;23(9):774\u20139.","journal-title":"Seizure."},{"issue":"1","key":"9541_CR10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/cge.14074","volume":"101","author":"L Jain","year":"2022","unstructured":"Jain L, Oberman LM, Beamer L, Cascio L, May M, Srikanth S, et al. Genetic and metabolic profiling of individuals with Phelan-McDermid syndrome presenting with seizures. Clin Genet. 2022;101(1):87\u2013100.","journal-title":"Clin Genet"},{"issue":"4","key":"9541_CR11","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/hmg\/ddab280","volume":"31","author":"T Levy","year":"2022","unstructured":"Levy T, Foss-Feig JH, Betancur C, Siper PM, Trelles-Thorne MDP, Halpern D, et al. Strong evidence for genotype-phenotype correlations in Phelan-McDermid syndrome: results from the developmental synaptopathies consortium. Hum Mol Genet. 2022;31(4):625\u201337.","journal-title":"Hum Mol Genet"},{"issue":"5","key":"9541_CR12","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"key":"9541_CR13","volume-title":"(ADOS-2) Manual (Part I): modules 1\u20134. Autism Diagnostic Observation Schedule","author":"C Lord","year":"2012","unstructured":"Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop S, Gutrie W. (ADOS-2) Manual (Part I): modules 1\u20134. Autism diagnostic observation schedule. 2012."},{"issue":"5","key":"9541_CR14","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/BF02172145","volume":"24","author":"C Lord","year":"1994","unstructured":"Lord C, Rutter M, Le Couteur A. Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord. 1994;24(5):659\u201385.","journal-title":"J Autism Dev Disord"},{"key":"9541_CR15","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. Diagnostic and statistical manual of mental disorders : DSM-5. American Psychiatric A, American Psychiatric Association DSMTF, editors. Arlington: American Psychiatric Association; 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"issue":"4","key":"9541_CR16","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/epi.13670","volume":"58","author":"RS Fisher","year":"2017","unstructured":"Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522\u201330.","journal-title":"Epilepsia"},{"key":"9541_CR17","unstructured":"Mullen EM. Mullen scales of early learning manual: American Guidance Service. 1995."},{"key":"9541_CR18","unstructured":"Roid GH, Pomplun M. The stanford-binet intelligence scales: The Guilford Press. 2012."},{"key":"9541_CR19","unstructured":"Elliot C. Differential abilities scale\u20142nd edition (DAS-II) manual. Harcourt Assessment. 2007."},{"issue":"2","key":"9541_CR20","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1159\/000503831","volume":"54","author":"E Beghi","year":"2019","unstructured":"Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology. 2019;54(2):185\u201391.","journal-title":"Neuroepidemiology"},{"issue":"1","key":"9541_CR21","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.braindev.2020.08.014","volume":"43","author":"D Samanta","year":"2021","unstructured":"Samanta D. Epilepsy in Angelman syndrome: a scoping review. Brain Dev. 2021;43(1):32\u201344.","journal-title":"Brain Dev"},{"key":"9541_CR22","doi-asserted-by":"publisher","first-page":"106813","DOI":"10.1016\/j.yebeh.2019.106813","volume":"103","author":"IN Mohamed","year":"2020","unstructured":"Mohamed IN, Osman AH, Mohamed S, Hamid EK, Hamed AA, Alsir A, et al. Intelligence quotient (IQ) among children with epilepsy: National epidemiological study \u2013 Sudan. Epilepsy Behav. 2020;103:106813.","journal-title":"Epilepsy Behav"},{"key":"9541_CR23","doi-asserted-by":"publisher","first-page":"746381","DOI":"10.3389\/fneur.2021.746381","volume":"12","author":"H Gauffin","year":"2021","unstructured":"Gauffin H, Landtblom AM, Vigren P, Frick A, Engstr\u00f6m M, McAllister A, Karlsson T. Similar profile and magnitude of cognitive impairments in focal and generalized epilepsy: a pilot study. Front Neurol. 2021;12:746381.","journal-title":"Front Neurol"},{"key":"9541_CR24","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.seizure.2016.09.002","volume":"44","author":"M Sillanp\u00e4\u00e4","year":"2017","unstructured":"Sillanp\u00e4\u00e4 M, Schmidt D. Long-term outcome of medically treated epilepsy. Seizure. 2017;44:211\u20136.","journal-title":"Seizure"},{"issue":"1","key":"9541_CR25","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/epi.13604","volume":"58","author":"DJ Thurman","year":"2017","unstructured":"Thurman DJ, Logroscino G, Beghi E, Hauser WA, Hesdorffer DC, Newton CR, et al. The burden of premature mortality of epilepsy in high-income countries: a systematic review from the Mortality Task Force of the International League Against Epilepsy. Epilepsia. 2017;58(1):17\u201326.","journal-title":"Epilepsia"}],"container-title":["Journal of Neurodevelopmental Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s11689-024-09541-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s11689-024-09541-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s11689-024-09541-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:02:06Z","timestamp":1715338926000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneurodevdisorders.biomedcentral.com\/articles\/10.1186\/s11689-024-09541-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,10]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["9541"],"URL":"https:\/\/doi.org\/10.1186\/s11689-024-09541-0","relation":{},"ISSN":["1866-1955"],"issn-type":[{"type":"electronic","value":"1866-1955"}],"subject":[],"published":{"date-parts":[[2024,5,10]]},"assertion":[{"value":"4 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Boston Children\u2019s Hospital Institutional Review Board (IRB) approved the study, serving as the central IRB for all the participating study sites. Caregivers or legal guardians of the participants provided informed consent and assent was obtained when applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}