{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:27:12Z","timestamp":1791804432017,"version":"4.3.4"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>Potocki\u2013Shaffer syndrome (PSS) is a rare neurodevelopmental disorder caused by deletions involving the 11p11.2-p12 region, encompassing the plant homeodomain finger protein 21A (<jats:italic toggle=\"yes\">PHF21A<\/jats:italic>) gene. <jats:italic toggle=\"yes\">PHF21A<\/jats:italic> has an important role in epigenetic regulation and <jats:italic toggle=\"yes\">PHF21A<\/jats:italic> variants have previously been associated with a specific disorder that, whilst sharing some features of PSS, has notable differences. This study aims to expand the phenotype, particularly in relation to overgrowth, associated with <jats:italic toggle=\"yes\">PHF21A<\/jats:italic> variants. Analysis of phenotypic data was undertaken on 13 individuals with <jats:italic toggle=\"yes\">PHF21A<\/jats:italic> constitutional variants including four individuals described in the current series. Of those individuals where data were recorded, postnatal overgrowth was reported in 5\/6 (83%). In addition, all had both an intellectual disability and behavioural issues. Frequent associations included postnatal hypotonia (7\/11, 64%); and at least one afebrile seizure episode (6\/12, 50%). Although a recognizable facial gestalt was not associated, subtle dysmorphic features were shared amongst some individuals and included a tall broad forehead, broad nasal tip, anteverted nares and full cheeks. We provide further insight into the emerging neurodevelopmental syndrome associated with PHF21A disruption. We present some evidence that <jats:italic toggle=\"yes\">PHF21A<\/jats:italic> might be considered a new member of the overgrowth-intellectual disability syndrome (OGID) family.<\/jats:p>","DOI":"10.1097\/mcd.0000000000000455","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T09:01:46Z","timestamp":1678093306000},"page":"49-54","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["The PHF21A neurodevelopmental disorder: an evaluation of clinical data from 13 patients"],"prefix":"10.1097","volume":"32","author":[{"given":"Rebecca L.","family":"Poole","sequence":"first","affiliation":[{"name":"South East of Scotland Clinical Genetics Service, Western General Hospital, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia K.","family":"Bijlsma","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Houge","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Jones","sequence":"additional","affiliation":[{"name":"Nottingham Clinical Genetics Service, Nottingham City Hospital, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Mik\u0161tien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egl\u0117","family":"Preik\u0161aitien\u0117","sequence":"additional","affiliation":[{"name":"Department of Human and Medical Genetics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Thompson","sequence":"additional","affiliation":[{"name":"South East of Scotland Clinical Genetics Service, Western General Hospital, Edinburgh, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Tatton-Brown","sequence":"additional","affiliation":[{"name":"St George\u2019s University of London"},{"name":"South West Thames Regional Genetics Department, St George\u2019s University Hospitals NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"R1-20250524","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ajhg.2020.01.019","article-title":"Evaluation of DNA methylation episignatures for diagnosis and phenotype correlations in 42 mendelian neurodevelopmental disorders.","volume":"106","author":"Aref-Eshghi","year":"2020","journal-title":"Am J Hum Genet"},{"key":"R2-20250524","first-page":"734","article-title":"Delineation of a contiguous gene syndrome with multiple exostoses, enlarged parietal foramina, craniofacial dysostosis, and mental retardation, caused by deletions in the short arm of chromosome 11.","volume":"58","author":"Bartsch","year":"1996","journal-title":"Am J Hum Genet"},{"key":"R3-20250524","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/(SICI)1097-0258(19980228)17:4<407::AID-SIM742>3.0.CO;2-L","article-title":"British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood.","volume":"17","author":"Cole","year":"1998","journal-title":"Stat Med"},{"key":"R5-20250524","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/adc.73.1.17","article-title":"Cross sectional stature and weight reference curves for the UK, 1990.","volume":"73","author":"Freeman","year":"1995","journal-title":"Arch Dis Child"},{"key":"R6-20250524","doi-asserted-by":"crossref","first-page":"7420","DOI":"10.1073\/pnas.112008599","article-title":"A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes.","volume":"99","author":"Hakimi","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"R7-20250524","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/s41431-018-0289-x","article-title":"De novo truncating variants in PHF21A cause intellectual disability and craniofacial anomalies.","volume":"27","author":"Hamanaka","year":"2019","journal-title":"Eur J Hum Genet"},{"key":"R8-20250524","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.bbrc.2004.07.163","article-title":"Characterization of BHC80 in BRAF-HDAC complex, involved in neuron-specific gene repression.","volume":"322","author":"Iwase","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"R9-20250524","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ajhg.2012.05.005","article-title":"Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies.","volume":"91","author":"Kim","year":"2012","journal-title":"Am J Hum Genet"},{"key":"R10-20250524","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13229-019-0286-0","article-title":"Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism.","volume":"10","author":"Kim","year":"2019","journal-title":"Mol Autism"},{"key":"R11-20250524","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1002\/ajmg.a.37344","article-title":"A microdeletion encompassing PHF21A in an individual with global developmental delay and craniofacial anomalies.","volume":"167","author":"Labonne","year":"2015","journal-title":"Am J Med Genet A"},{"key":"R12-20250524","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nature04021","article-title":"An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation.","volume":"437","author":"Lee","year":"2005","journal-title":"Nature"},{"key":"R13-20250524","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/ajmg.a.37988","article-title":"Potocki-Shaffer syndrome in a child without intellectual disability \u2013 the role of PHF21A in cognitive function.","volume":"173","author":"Mccool","year":"2017","journal-title":"Am J Med Genet A"},{"key":"R14-20250524","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/ajmg.a.35671","article-title":"A 137-kb deletion within the Potocki\u2013Shaffer syndrome interval on chromosome 11p11.2 associated with developmental delay and hypotonia.","volume":"161","author":"Montgomery","year":"2013","journal-title":"Am J Med Genet A"},{"key":"R15-20250524","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<319::AID-AJMG22>3.0.CO;2-M","article-title":"Interstitial deletion of 11(p11.2p12): a newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses (EXT2).","volume":"62","author":"Potocki","year":"1996","journal-title":"Am J Med Genet"},{"key":"R16-20250524","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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.","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"R17-20250524","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/ajmg.1320450512","article-title":"Familial interstitial deletion 11(p11.12p12) associated with parietal foramina, brachymicrocephaly, and mental retardation.","volume":"45","author":"Shaffer","year":"1993","journal-title":"Am J Med Genet"},{"key":"R18-20250524","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/ajmg.a.33245","article-title":"Potocki-Shaffer syndrome: comprehensive clinical assessment, review of the literature, and proposals for medical management.","volume":"152a","author":"Swarr","year":"2010","journal-title":"Am J Med Genet A"},{"key":"R19-20250524","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.ajhg.2017.03.010","article-title":"Mutations in epigenetic regulation genes are a major cause of overgrowth with intellectual disability.","volume":"100","author":"Tatton-Brown","year":"2017","journal-title":"Am J Hum Genet"},{"key":"R20-20250524","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/ajmg.c.31362","article-title":"Molecular mechanisms of childhood overgrowth.","volume":"163c","author":"Tatton-Brown","year":"2013","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"R21-20250524","doi-asserted-by":"crossref","first-page":"788","DOI":"10.3390\/brainsci10110788","article-title":"New insights into Potocki-Shaffer syndrome: report of two novel cases and literature review.","volume":"10","author":"Trajkova","year":"2020","journal-title":"Brain Sci"},{"key":"R22-20250524","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1016\/S0140-6736(14)61705-0","article-title":"Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data.","volume":"385","author":"Wright","year":"2015","journal-title":"Lancet"}],"container-title":["Clinical Dysmorphology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000455","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T20:01:42Z","timestamp":1748116902000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1097\/mcd.0000000000000455","relation":{},"ISSN":["0962-8827"],"issn-type":[{"value":"0962-8827","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}