{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:12:10Z","timestamp":1789431130496,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Phelan\u2013McDermid syndrome (PMS), caused by deletions at 22q13.3 and pathogenic variants in the <jats:italic>SHANK3<\/jats:italic> gene, is a rare developmental disorder characterized by hypotonia, developmental delay (DD), intellectual disability (ID), autism spectrum disorder (ASD), dysmorphic features, absence of or delayed language, and other features.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Conventional karyotyping, chromosomal microarray analysis (CMA), and whole exome sequencing (WES) have been used to detect genetic defects causing PMS. We summarized the genetic and clinical findings from prenatal to postnatal stages of detected cases of PMS and mapped potential candidate haploinsufficient genes for deletions of 22q13. This study aimed to summarize the laboratory findings, genetic defects, and genotype\u2013phenotype correlations for Chinese patients with PMS.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Seven prenatal cases and fourteen postnatal cases were diagnosed with PMS in our center. Thirteen cases had a deletion ranging in size from 69 to 9.06\u00a0Mb at 22q13.2-q13.33, and five cases had a pathogenic variant or an intragenic deletion in the <jats:italic>SHANK3<\/jats:italic> gene. Three familial cases with a parental carrier of a balanced translocation were noted. A review of the literature noted another case series of 29 cases and a report of five cases of PMS in China. Genotype\u2013phenotype correlations confirmed haploinsufficiency of the <jats:italic>SHANK3<\/jats:italic> gene for PMS and suggested other candidate haploinsufficient genes <jats:italic>TNFRSFI3C<\/jats:italic> and <jats:italic>NFAM1<\/jats:italic> genes for immunological features and <jats:italic>TCF20, SULT4A1<\/jats:italic>, <jats:italic>PARVB, SCO2<\/jats:italic>, and <jats:italic>UPK3A<\/jats:italic> genes for intellectual impairment and behavioral abnormality, neurological features, macrocephaly\/hypotonia, oculopathy, and renal adysplasia, respectively.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Indications for prenatal diagnosis of PMS are not specific, and approximately 85% prenatally diagnosed PMS elected termination of pregnancies after genetic counseling. For postnatal cases, 62.5% were caused by a deletion at 22q13 and 37.5% were caused by a pathogenic variant or an intragenic deletion in the <jats:italic>SHANK3<\/jats:italic> gene. Approximately 6.7% of cases with a deletion were familial, and almost all pathogenic variants were <jats:italic>de novo<\/jats:italic>. Combined karyotype, CMA, and WES should be performed to increase the diagnostic yield. The identification of other candidate haploinsufficient genes in deletions of 22q13.2-q13.33 could relate to more severe dysmorphic features, neurologic defects, and immune deficiency. These results provided evidence for diagnostic interpretation, genetic counseling, and clinical management for the Chinese cases of PMS.<\/jats:p>","DOI":"10.3389\/fgene.2022.961196","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T06:02:04Z","timestamp":1661925724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Prenatal and postnatal diagnosis of Phelan\u2013McDermid syndrome: A report of 21 cases from a medical center and review of the literature"],"prefix":"10.3389","volume":"13","author":[{"given":"Ying","family":"Hao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuwei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peining","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansheng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1038\/sj.ejhg.5201369","article-title":"A 2.3 Mb duplication of chromosome 8q24.3 associated with severe mental retardation and epilepsy detected by standard karyotype","volume":"13","author":"Bonaglia","year":"2005","journal-title":"Eur. 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