{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T04:25:19Z","timestamp":1742358319906,"version":"3.40.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Phelan\u2013McDermid syndrome (PMS) is a neurodevelopmental disorder, caused by haploinsufficiency of the <jats:italic>SHANK3<\/jats:italic> gene. In addition to global developmental delay (GDD)\/intellectual disability (ID) and autism spectrum disorder (ASD), PMS is characterized by multiple neurologic, behavioral and multisystemic manifestations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We aimed to establish a database of individuals with PMS in Israel. All participants underwent a detailed evaluation at a single medical center, and demographic, clinical, and genetic data were collected.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Seventeen unrelated individuals with PMS (mean age 10\u2009\u00b1\u20098.2 years; range, 2.5\u201336 years) were enrolled (10 females, 59%), all of Jewish descent. Twelve cases (70%) were caused by deletions in chromosomal region 22q13.3, including mosaicism, ring chromosome and unbalanced translocation. The other 5 (30%) cases were due to single nucleotide variants (SNVs), while the de novo SNV c.3904dup (p.Ala1302GlyfsTer69), recurred in 3 cases. All 17 participants had GDD\/ID (which was severe in 10, 59%), and ASD and seizures were present in 12 (70%) and 8 (47%) individuals, respectively. Additional frequent manifestations were sleep difficulties in 13 individuals (76%), bowel movement disorders in 13 (76%), urinary track involvement in 8 (47%) and endocrine disorders in 6 (35%). Abnormal but nonspecific findings on prenatal ultrasonography were noted in 3 participants (18%). The most common perinatal complication was prolonged jaundice in 5 infants (29%). Different medical treatment modalities, including cannabidiol (CBD) full-spectrum oil extracts, were used to ease symptoms, with variable results.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our experience adds to current knowledge about clinical manifestations and potential symptomatic treatment of PMS in Israel. These findings may promote clinical research and serve as infrastructure for future clinical trials.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-03598-3","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T11:29:19Z","timestamp":1742297359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical profiling and medical management of Israeli individuals with Phelan McDermid syndrome"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-0732","authenticated-orcid":false,"given":"Odelia","family":"Chorin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lior","family":"Greenbaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelly","family":"Lev-Hochberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neta","family":"Feinstein-Goren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aviva","family":"Eliyahu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagit","family":"Shani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elon","family":"Pras","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tal","family":"Weissbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoav","family":"Bolkier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gali","family":"Heimer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorit","family":"Lev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Michelson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Regev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sagi","family":"Josefsberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nurit Assia","family":"Batzir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adel","family":"Shalata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronen","family":"Spiegel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reeval","family":"Segel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orit","family":"Lobel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bassam","family":"Abu-Libdeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mordechai","family":"Shohat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Frydman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronen","family":"Hady-Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Pode-Shakked","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Rein-Rothschild","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"3598_CR1","doi-asserted-by":"publisher","first-page":"961196","DOI":"10.3389\/fgene.2022.961196","volume":"13","author":"Y Hao","year":"2022","unstructured":"Hao Y, Liu Y, Yang J, Li X, Luo F, Geng Q, Li S, Li P, Wu W, Xie J. Prenatal and postnatal diagnosis of Phelan-McDermid syndrome: a report of 21 cases from a medical center and review of the literature. Front Genet. 2022;13:961196.","journal-title":"Front Genet"},{"issue":"1","key":"3598_CR2","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1866-1955-6-39","volume":"6","author":"A Kolevzon","year":"2014","unstructured":"Kolevzon A, Angarita B, Bush L, Wang AT, Frank Y, Yang A, Rapaport R, Saland J, Srivastava S, Farrell C, Edelmann LJ, Buxbaum JD. Phelan-McDermid syndrome: a review of the literature and practice parameters for medical assessment and monitoring. J Neurodev Disord. 2014;6(1):39.","journal-title":"J Neurodev Disord"},{"issue":"3\u20135","key":"3598_CR3","first-page":"186","volume":"2","author":"K Phelan","year":"2012","unstructured":"Phelan K, McDermid HE. The 22q13.3 deletion syndrome (Phelan-McDermid syndrome). Mol Syndromol. 2012;2(3\u20135):186\u2013201.","journal-title":"Mol Syndromol"},{"key":"3598_CR4","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, Bel-Fenell\u00f3s C, Mori M\u00c1, Mil\u00e1 M, Del Campo M, Barr\u00faz P, Santos-Simarro F, Obreg\u00f3n G, Orellana C, Pachajoa H, Tenorio JA, Gal\u00e1n E, Cigudosa JC, Moresco A, Saleme C, Castillo S, Gabau E, P\u00e9rez-Jurado L, Barcia A, Mart\u00edn MS, Mansilla E, Vallcorba I, Garc\u00eda-Murillo P, Cammarata-Scalisi F, Gon\u00e7alves Pereira N, Blanco-Lago R, Serrano M, Ortigoza-Escobar JD, Gener B, Seidel VA, Tirado P, Lapunzina P. Spanish PMS Working Group. Variability in Phelan-McDermid syndrome in a cohort of 210 individuals. Front Genet. 2022;13:652454.","journal-title":"Front Genet"},{"issue":"7","key":"3598_CR5","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, Rogers RC, Phelan K, DuPont BR. Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome. Hum Genet. 2014;133(7):847\u201359.","journal-title":"Hum Genet"},{"key":"3598_CR6","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13229-018-0205-9","volume":"9","author":"S De Rubeis","year":"2018","unstructured":"De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018;9:31.","journal-title":"Mol Autism"},{"key":"3598_CR7","unstructured":"Phelan K, Rogers RC, Boccuto L, Phelan-McDermid S. 2005 May 11 [updated 2018 Jun 7]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132024."},{"issue":"5760","key":"3598_CR8","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1126\/science.1118995","volume":"311","author":"MK Baron","year":"2006","unstructured":"Baron MK, Boeckers TM, Vaida B, Faham S, Gingery M, Sawaya MR, Salyer D, Gundelfinger ED, Bowie JU. An architectural framework that may lie at the core of the postsynaptic density. Science. 2006;311(5760):531\u20135.","journal-title":"Science"},{"issue":"1","key":"3598_CR9","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/ng1933","volume":"39","author":"CM Durand","year":"2007","unstructured":"Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckars\u00e4ter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rog\u00e9 B, H\u00e9ron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39(1):25\u20137.","journal-title":"Nat Genet"},{"issue":"1","key":"3598_CR10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/ajmg.a.35700","volume":"161A","author":"KA Aldinger","year":"2013","unstructured":"Aldinger KA, Kogan J, Kimonis V, Fernandez B, Horn D, Klopocki E, Chung B, Toutain A, Weksberg R, Millen KJ, Barkovich AJ, Dobyns WB. Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet A. 2013;161A(1):131\u20136.","journal-title":"Am J Med Genet A"},{"issue":"2","key":"3598_CR11","doi-asserted-by":"publisher","first-page":"e376","DOI":"10.1542\/peds.2007-2584","volume":"122","author":"A Philippe","year":"2008","unstructured":"Philippe A, Boddaert N, Vaivre-Douret L, Robel L, Danon-Boileau L, Malan V, de Blois MC, Heron D, Colleaux L, Golse B, Zilbovicius M, Munnich A. Neurobehavioral profile and brain imaging study of the 22q13.3 deletion syndrome in childhood. Pediatrics. 2008;122(2):e376\u201382.","journal-title":"Pediatrics"},{"key":"3598_CR12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.pediatrneurol.2018.09.008","volume":"90","author":"S Srivastava","year":"2019","unstructured":"Srivastava S, Scherrer B, Prohl AK, Filip-Dhima R, Kapur K, Kolevzon A, Buxbaum JD, Berry-Kravis E, Soorya L, Thurm A, Powell CM, Bernstein JA, Warfield SK, Sahin M. Developmental synaptopathies Consortium. Volumetric analysis of the basal ganglia and cerebellar structures in patients with Phelan-McDermid syndrome. Pediatr Neurol. 2019;90:37\u201343.","journal-title":"Pediatr Neurol"},{"issue":"1","key":"3598_CR13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/pd.517","volume":"23","author":"CP Chen","year":"2003","unstructured":"Chen CP, Chern SR, Chang TY, Lee CC, Chen LF, Tzen CY, Wang W, Lin CJ, Yang BP, Yang LS. Prenatal diagnosis of mosaic ring chromosome 22 associated with cardiovascular abnormalities and intrauterine growth restriction. Prenat Diagn. 2003;23(1):40\u20133.","journal-title":"Prenat Diagn"},{"issue":"8","key":"3598_CR14","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/pd.955","volume":"24","author":"J Delc\u00e1n","year":"2004","unstructured":"Delc\u00e1n J, Orera M, Linares R, Saavedra D, Palomar A. A case of ring chromosome 22 with deletion of the 22q13.3 region associated with agenesis of the corpus callosum, fornix and septum pellucidum. Prenat Diagn. 2004;24(8):635\u20137.","journal-title":"Prenat Diagn"},{"issue":"10","key":"3598_CR15","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1002\/pd.2110","volume":"28","author":"S Maitz","year":"2008","unstructured":"Maitz S, Gentilin B, Colli AM, Rizzuti T, Brandolisio E, Vetro A, Zuffardi O, Guerneri S, Lalatta F. Expanding the phenotype of 22q13.3 deletion: report of a case detected prenatally. Prenat Diagn. 2008;28(10):978\u201380.","journal-title":"Prenat Diagn"},{"issue":"1","key":"3598_CR16","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1002\/(SICI)1097-0223(200001)20:1<76::AID-PD752>3.0.CO;2-M","volume":"20","author":"M Riegel","year":"2000","unstructured":"Riegel M, Baumer A, Wisser J, Acherman J, Schinzel A. Prenatal diagnosis of mosaicism for a Del(22)(q13). Prenat Diagn. 2000;20(1):76\u20139.","journal-title":"Prenat Diagn"},{"issue":"2","key":"3598_CR17","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1002\/1096-8628(20010615)101:2<91::AID-AJMG1340>3.0.CO;2-C","volume":"101","author":"MC Phelan","year":"2001","unstructured":"Phelan MC, Rogers RC, Saul RA, Stapleton GA, Sweet K, McDermid H, Shaw SR, Claytor J, Willis J, Kelly DP. 22q13 deletion syndrome. Am J Med Genet. 2001;101(2):91\u20139.","journal-title":"Am J Med Genet"},{"issue":"7","key":"3598_CR18","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1002\/ajmg.a.62222","volume":"185","author":"A Ricciardello","year":"2021","unstructured":"Ricciardello A, Tomaiuolo P, Persico AM. Genotype-phenotype correlation in Phelan-McDermid syndrome: a comprehensive review of chromosome 22q13 deleted genes. Am J Med Genet A. 2021;185(7):2211\u201333.","journal-title":"Am J Med Genet A"},{"issue":"1","key":"3598_CR19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/2040-2392-4-17","volume":"4","author":"C Betancur","year":"2013","unstructured":"Betancur C, Buxbaum JD. SHANK3 haploinsufficiency: a common but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders. Mol Autism. 2013;4(1):17.","journal-title":"Mol Autism"},{"issue":"3","key":"3598_CR20","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1007\/s13311-015-0352-z","volume":"12","author":"JL Costales","year":"2015","unstructured":"Costales JL, Kolevzon A. Phelan-McDermid Syndrome and SHANK3: implications for treatment. Neurotherapeutics. 2015;12(3):620\u201330.","journal-title":"Neurotherapeutics"},{"issue":"5","key":"3598_CR21","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, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee. 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":"3598_CR22","doi-asserted-by":"crossref","unstructured":"Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, Raca G, Ritter DI, South ST, Thorland EC, Pineda-Alvarez D, Aradhya S, Martin CL. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22(2):245\u2013257. Erratum in: Genet Med. 2021;23(11):2230.","DOI":"10.1038\/s41436-019-0686-8"},{"issue":"1","key":"3598_CR23","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/s41525-021-00254-0","volume":"6","author":"LO Loureiro","year":"2021","unstructured":"Loureiro LO, Howe JL, Reuter MS, Iaboni A, Calli K, Roshandel D, Priti\u0161anac I, Moses A, Forman-Kay JD, Trost B, Zarrei M, Rennie O, Lau LYS, Marshall CR, Srivastava S, Godlewski B, Buttermore ED, Sahin M, Hartley D, Frazier T, Vorstman J, Georgiades S, Lewis SME, Szatmari P, Bradley CAL, Tabet AC, Willems M, Lumbroso S, Piton A, Lespinasse J, Delorme R, Bourgeron T, Anagnostou E, Scherer SW. A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder. NPJ Genom Med. 2021;6(1):91.","journal-title":"NPJ Genom Med"},{"issue":"1","key":"3598_CR24","doi-asserted-by":"publisher","first-page":"19099","DOI":"10.1038\/s41598-021-98646-w","volume":"11","author":"B Pode-Shakked","year":"2021","unstructured":"Pode-Shakked B, Barel O, Singer A, Regev M, Poran H, Eliyahu A, Finezilber Y, Segev M, Berkenstadt M, Yonath H, Reznik-Wolf H, Gazit Y, Chorin O, Heimer G, Gabis LV, Tzadok M, Nissenkorn A, Bar-Yosef O, Zohar-Dayan E, Ben-Zeev B, Mor N, Kol N, Nayshool O, Shimshoviz N, Bar-Joseph I, Marek-Yagel D, Javasky E, Einy R, Gal M, Grinshpun-Cohen J, Shohat M, Dominissini D, Raas-Rothschild A, Rechavi G, Pras E, Greenbaum L. A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies. Sci Rep. 2021;11(1):19099.","journal-title":"Sci Rep"},{"issue":"1","key":"3598_CR25","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/s41398-023-02535-x","volume":"13","author":"Y Hussein","year":"2023","unstructured":"Hussein Y, Tripathi U, Choudhary A, Nayak R, Peles D, Rosh I, Rabinski T, Djamus J, Vatine GD, Spiegel R, Garin-Shkolnik T, Stern S. Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations. Transl Psychiatry. 2023;13(1):246.","journal-title":"Transl Psychiatry"},{"issue":"4","key":"3598_CR26","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, Frank Y, Lozano R, Layton C, Britvan B, Bernstein JA, Buxbaum JD, Berry-Kravis E, Powell CM, Srivastava S, Sahin M, Soorya L, Thurm A, Kolevzon A. Developmental synaptopathies Consortium. 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"},{"key":"3598_CR27","doi-asserted-by":"publisher","first-page":"829825","DOI":"10.5402\/2011\/829825","volume":"2011","author":"F Jafri","year":"2011","unstructured":"Jafri F, Fink J, Higgins RR, Tervo R. 22q13.32 deletion and duplication and inversion in the same family: a rare occurrence. ISRN Pediatr. 2011;2011:829825.","journal-title":"ISRN Pediatr"},{"issue":"1","key":"3598_CR28","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/MCD.0b013e3281c1c81d","volume":"17","author":"M Tagaya","year":"2008","unstructured":"Tagaya M, Mizuno S, Hayakawa M, Yokotsuka T, Shimizu S, Fujimaki H. Recombination of a maternal pericentric inversion results in 22q13 deletion syndrome. Clin Dysmorphol. 2008;17(1):19\u201321.","journal-title":"Clin Dysmorphol"},{"key":"3598_CR29","doi-asserted-by":"crossref","unstructured":"Koza SA, Tabet AC, Bonaglia MC, Andres S, Anderlid BM, Aten E, Stiefsohn D; European Phelan-McDermid syndrome consortium; Evans DG, van Ravenswaaij-Arts CMA, Kant SG. Consensus recommendations on counseling in Phelan-McDermid syndrome, with special attention to recurrence risk and to ring chromosome 22. Eur J Med Genet. 2023;66(7):104773.","DOI":"10.1016\/j.ejmg.2023.104773"},{"key":"3598_CR30","doi-asserted-by":"publisher","unstructured":"Samogy-Costa C, Varella-Branco E, Monfardini F, Ferraz H, Fock R, Barbosa R, Pessoa A, Perez A, Louren\u00e7o N, Vibranovski M, Krepischi A, Rosenberg C, Passos-Bueno M. A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype-phenotype correlation and identification of an atypical case. J Neurodevelopmental Disorders. 2019;11. https:\/\/doi.org\/10.1186\/s11689-019-9273-1.","DOI":"10.1186\/s11689-019-9273-1"},{"issue":"8","key":"3598_CR31","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, Bernstein JA, Asante-Otoo A, Bennett WE Jr, Betancur C, Brickhouse TH, Passos Bueno MR, Chopra M, Christensen CK, Cully JL, Dies K, Friedman K, Gummere B, Holder JL Jr, Jimenez-Gomez A, Kerins CA, Khan O, Kohlenberg T, Lacro RV, Levi LA, Levy T, Linnehan D, Eva L, Moshiree B, Neumeyer A, Paul SM, Phelan K, Persico A, Rapaport R, Rogers C, Saland J, Sethuram S, Shapiro J, Tarr PI, White KM, Wickstrom J, Williams KM, Winrow D, Wishart B, Kolevzon A. 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":"11","key":"3598_CR32","doi-asserted-by":"publisher","first-page":"104042","DOI":"10.1016\/j.ejmg.2020.104042","volume":"63","author":"CA Ziats","year":"2020","unstructured":"Ziats CA, Jain L, McLarney B, Vandenboom E, DuPont BR, Rogers C, Sarasua S, Nevado J, Cordisco EL, Phelan K, Boccuto L. Neurofibromatosis type 2 in Phelan-McDermid syndrome: institutional experience and review of the literature. Eur J Med Genet. 2020;63(11):104042.","journal-title":"Eur J Med Genet"},{"issue":"3","key":"3598_CR33","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ejhg.2012.175","volume":"21","author":"L Boccuto","year":"2013","unstructured":"Boccuto L, Lauri M, Sarasua SM, Skinner CD, Buccella D, Dwivedi A, Orteschi D, Collins JS, Zollino M, Visconti P, DuPont B, Tiziano D, Schroer RJ, Neri G, Stevenson RE, Gurrieri F, Schwartz CE. Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders. Eur J Hum Genet. 2013;21(3):310\u20136.","journal-title":"Eur J Hum Genet"},{"key":"3598_CR34","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1101\/gr.148718.112","volume":"23","author":"SB Montgomery","year":"2013","unstructured":"Montgomery SB, et al. The origin, evolution, and functional impact of short insertion\u2013deletion variants identified in 179 human genomes. Genome Res. 2013;23:749\u201361.","journal-title":"Genome Res"},{"key":"3598_CR35","doi-asserted-by":"publisher","first-page":"103283","DOI":"10.1038\/nrg2820","volume":"11","author":"M Swami","year":"2010","unstructured":"Swami M, Mutation. It\u2019s the CpG content that counts. Nat Rev Genet. 2010;11:103283.","journal-title":"Nat Rev Genet"},{"key":"3598_CR36","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.brainres.2010.11.005","volume":"1380","author":"A Kolevzon","year":"2011","unstructured":"Kolevzon A, Cai G, Soorya L, Takahashi N, Grodberg D, Kajiwara Y, Willner JP, Tryfon A, Buxbaum JD. Analysis of a purported SHANK3 mutation in a boy with autism: clinical impact of rare variant research in neurodevelopmental disabilities. Brain Res. 2011;1380:98\u2013105.","journal-title":"Brain Res"},{"issue":"3","key":"3598_CR37","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.tjog.2016.05.003","volume":"55","author":"CP Chen","year":"2016","unstructured":"Chen CP, Chang TY, Wang LK, Chern SR, Wu PS, Chen YN, Chen SW, Chen WL, Wang W. 22q13 deletion syndrome in a fetus associated with microtia, hemivertebrae, and congenital heart defects on prenatal ultrasound. Taiwan J Obstet Gynecol. 2016;55(3):455\u20136.","journal-title":"Taiwan J Obstet Gynecol"},{"issue":"1","key":"3598_CR38","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1186\/s13023-020-01592-5","volume":"15","author":"N Xu","year":"2020","unstructured":"Xu N, Lv H, Yang T, Du X, Sun Y, Xiao B, Fan Y, Luo X, Zhan Y, Wang L, Li F, Yu Y. A 29 mainland Chinese cohort of patients with Phelan-McDermid syndrome: genotype-phenotype correlations and the role of SHANK3 haploinsufficiency in the important phenotypes. Orphanet J Rare Dis. 2020;15(1):335.","journal-title":"Orphanet J Rare Dis"},{"issue":"2","key":"3598_CR39","doi-asserted-by":"publisher","first-page":"e20191490","DOI":"10.1542\/peds.2019-1490","volume":"145","author":"L Alexandra","year":"2020","unstructured":"Alexandra L, Bey MP, Gorman W, Gallentine TM, Kohlenberg. Jennifer Frankovich, Yong-Hui Jiang, Keith Van Haren; Subacute Neuropsychiatric Syndrome in girls with SHANK3 mutations responds to Immunomodulation. Pediatrics. 2020;145(2):e20191490.","journal-title":"Pediatrics"},{"issue":"2","key":"3598_CR40","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1097\/MCD.0000000000000296","volume":"29","author":"P Cianci","year":"2020","unstructured":"Cianci P, Pezzoli L, Maitz S, Agosti M, Iascone M, Selicorni A. Dual genetic diagnoses: neurofibromatosis type 1 and KBG syndrome. Clin Dysmorphol. 2020;29(2):101\u20133.","journal-title":"Clin Dysmorphol"},{"issue":"2","key":"3598_CR41","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/bjh.16967","volume":"191","author":"F Saettini","year":"2020","unstructured":"Saettini F, L\u2019Imperio V, Fazio G, Cazzaniga G, Mazza C, Moroni I, Badolato R, Biondi A, Corti P. More than an \u2018atypical\u2019 phenotype: dual molecular diagnosis of autoimmune lymphoproliferative syndrome and Becker muscular dystrophy. Br J Hematol. 2020;191(2):291\u20134.","journal-title":"Br J Hematol"},{"issue":"1","key":"3598_CR42","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1097\/MCD.0b013e32833effb1","volume":"20","author":"BE Kirkpatrick","year":"2011","unstructured":"Kirkpatrick BE, El-Khechen D. A unique presentation of 22q13 deletion syndrome: multicystic kidney, orofacial clefting, and Wilms\u2019 tumor. Clin Dysmorphol. 2011;20(1):53\u20134.","journal-title":"Clin Dysmorphol"},{"issue":"5","key":"3598_CR43","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1111\/j.1447-0756.2009.01040.x","volume":"35","author":"A Ko\u00e7","year":"2009","unstructured":"Ko\u00e7 A, Arisoy O, Pala E, Erdem M, Kaymak AO, Erkal O, Karao\u011fuz MY. Prenatal diagnosis of mosaic ring 22 duplication\/deletion with terminal 22q13 deletion due to abnormal first trimester screening and choroid plexus cyst detected on ultrasound. J Obstet Gynecol Res. 2009;35(5):978\u201382.","journal-title":"J Obstet Gynecol Res"},{"issue":"3","key":"3598_CR44","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s00467-023-06146-y","volume":"39","author":"MD McCoy","year":"2024","unstructured":"McCoy MD, Sarasua SM, DeLuca JM, Davis S, Rogers RC, Phelan K, Boccuto L. Genetics of kidney disorders in Phelan-McDermid syndrome: evidence from 357 registry participants. Pediatr Nephrol. 2024;39(3):749\u201360.","journal-title":"Pediatr Nephrol"},{"issue":"3","key":"3598_CR45","doi-asserted-by":"publisher","first-page":"504","DOI":"10.3390\/genes13030504","volume":"13","author":"F Cammarata-Scalisi","year":"2022","unstructured":"Cammarata-Scalisi F, Callea M, Martinelli D, Willoughby CE, Tadich AC, Araya Castillo M, Lacruz-Rengel MA, Medina M, Grimaldi P, Bertini E, Nevado J. Clinical and genetic aspects of Phelan-McDermid syndrome: an Interdisciplinary Approach to Management. Genes (Basel). 2022;13(3):504.","journal-title":"Genes (Basel)"},{"issue":"1","key":"3598_CR46","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s13229-021-00459-1","volume":"12","author":"J Fastman","year":"2021","unstructured":"Fastman J, Foss-Feig J, Frank Y, Halpern D, Harony-Nicolas H, Layton C, Sandin S, Siper P, Tang L, Trelles P, Zweifach J, Buxbaum JD, Kolevzon A. A randomized controlled trial of intranasal oxytocin in Phelan-McDermid syndrome. Mol Autism. 2021;12(1):62.","journal-title":"Mol Autism"},{"issue":"1","key":"3598_CR47","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13229-022-00493-7","volume":"13","author":"A Kolevzon","year":"2022","unstructured":"Kolevzon A, Breen MS, Siper PM, Halpern D, Frank Y, Rieger H, Weismann J, Trelles MP, Lerman B, Rapaport R, Buxbaum JD. Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome. Mol Autism. 2022;13(1):17.","journal-title":"Mol Autism"},{"issue":"1","key":"3598_CR48","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13229-022-00485-7","volume":"13","author":"S Sethuram","year":"2022","unstructured":"Sethuram S, Levy T, Foss-Feig J, Halpern D, Sandin S, Siper PM, Walker H, Buxbaum JD, Rapaport R, Kolevzon A. A proof-of-concept study of growth hormone in children with Phelan-McDermid syndrome. Mol Autism. 2022;13(1):6.","journal-title":"Mol Autism"},{"issue":"2","key":"3598_CR49","doi-asserted-by":"publisher","first-page":"490","DOI":"10.3390\/genes14020490","volume":"14","author":"BA Moffitt","year":"2023","unstructured":"Moffitt BA, Sarasua SM, Ivankovic D, Ward LD, Valentine K, Bennett WE Jr, Rogers C, Phelan K, Boccuto L. Stratification of a Phelan-McDermid Syndrome Population based on their response to human growth hormone and insulin-like growth factor. Genes (Basel). 2023;14(2):490.","journal-title":"Genes (Basel)"},{"issue":"1","key":"3598_CR50","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13229-020-00366-x","volume":"11","author":"N Perets","year":"2020","unstructured":"Perets N, Oron O, Herman S, Elliott E, Offen D. Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B. Mol Autism. 2020;11(1):65.","journal-title":"Mol Autism"},{"issue":"1","key":"3598_CR51","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1038\/s41598-018-37570-y","volume":"9","author":"L Bar-Lev Schleider","year":"2019","unstructured":"Bar-Lev Schleider L, Mechoulam R, Saban N, Meiri G, Novack V. Real life experience of Medical Cannabis Treatment in Autism: analysis of Safety and Efficacy. Sci Rep. 2019;9(1):200.","journal-title":"Sci Rep"},{"issue":"3\u20134","key":"3598_CR52","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1159\/000521683","volume":"107","author":"CA Legare","year":"2022","unstructured":"Legare CA, Raup-Konsavage WM, Vrana KE. Therapeutic potential of Cannabis, Cannabidiol, and cannabinoid-based pharmaceuticals. Pharmacology. 2022;107(3\u20134):131\u201349.","journal-title":"Pharmacology"},{"key":"3598_CR53","doi-asserted-by":"publisher","first-page":"18","DOI":"10.7812\/TPP\/18-041","volume":"23","author":"S Shannon","year":"2019","unstructured":"Shannon S, Lewis N, Lee H, Hughes S. Cannabidiol in anxiety and sleep: a large Case Series. Perm J. 2019;23:18\u2013041.","journal-title":"Perm J"},{"key":"3598_CR54","first-page":"e20200149","volume":"44","author":"EAD Silva","year":"2022","unstructured":"Silva EAD, Junior, Medeiros WMB, Torro N, Sousa JMM, Almeida IBCM, Costa FBD, Pontes KM, Nunes ELG, Rosa MDD, Albuquerque KLGD. Cannabis and cannabinoid use in autism spectrum disorder: a systematic review. Trends Psychiatry Psychother. 2022;44:e20200149.","journal-title":"Trends Psychiatry Psychother"},{"key":"3598_CR55","doi-asserted-by":"publisher","first-page":"1328885","DOI":"10.3389\/fphar.2023.1328885","volume":"14","author":"S Moniek Schouten","year":"2023","unstructured":"Moniek Schouten S, Dalle D, Mantini, Koppo K. Cannabidiol and brain function: current knowledge and future perspectives. Front Pharmacol. 2023;14:1328885.","journal-title":"Front Pharmacol"},{"key":"3598_CR56","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s42238-021-00078-w","volume":"3","author":"R Lucile Rapin","year":"2021","unstructured":"Lucile Rapin R, Gamaoun CE, Hage MF, Arboleda, Prosk E. Cannabidiol use and effectiveness: real-world evidence from a Canadian medical cannabis clinic. J Cannabis Res. 2021;3:19.","journal-title":"J Cannabis Res"},{"key":"3598_CR57","first-page":"18","volume":"23","author":"MD Scott Shannon","year":"2019","unstructured":"Scott Shannon MD, Nicole Lewis ND, Heather Lee PA-C, Hughes S. PhD. Cannabidiol in anxiety and sleep: a large Case Series. Perm J. 2019;23:18\u2013041.","journal-title":"Perm J"},{"key":"3598_CR58","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.schres.2022.12.033","volume":"252","author":"A Alkelai","year":"2023","unstructured":"Alkelai A, Greenbaum L, Shohat S, Povysil G, Malakar A, Ren Z, Motelow JE, Schechter T, Draiman B, Chitrit-Raveh E, Hughes D, Jobanputra V, Shifman S, Goldstein DB, Kohn Y. Genetic insights into childhood-onset schizophrenia: the yield of clinical exome sequencing. Schizophr Res. 2023;252:138\u201345.","journal-title":"Schizophr Res"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-03598-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-03598-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-03598-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T11:29:24Z","timestamp":1742297364000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-025-03598-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3598"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-03598-3","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]},"assertion":[{"value":"24 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2025","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 study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board (IRB) at Sheba Medical Center. The need for written informed consent to participate was waived.","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 have no competing interests to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}