{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:40Z","timestamp":1787894320548,"version":"build-2784847793"},"reference-count":70,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Polyaminopathies are a recently described family of rare genetic neurodevelopmental disorders. Polyaminopathies disrupt the biosynthesis of the primary polyamines: putrescine, spermidine, and spermine. Snyder\u2013Robinson syndrome results from hemizygous loss\u2010of\u2010function variants in the spermine synthase (\n                    <jats:italic>SMS<\/jats:italic>\n                    ) gene, resulting in decreased or complete loss of spermine synthase enzyme activity. Bachmann\u2013Bupp syndrome results from heterozygous gain\u2010of\u2010function variants in the ornithine decarboxylase 1 (\n                    <jats:italic>ODC1<\/jats:italic>\n                    ) gene, resulting in increased ornithine decarboxylase enzyme activity. Faundes\u2013Banka syndrome results from heterozygous loss\u2010of\u2010function variants in the eukaryotic translation initiation factor 5A (\n                    <jats:italic>EIF5A<\/jats:italic>\n                    ) gene, impairing eIF5A protein function. DHPS (deoxyhypusine synthase) deficiency is an autosomal recessive disease and results from bi\u2010allelic hypomorphic variants in the deoxyhypusine synthase (\n                    <jats:italic>DHPS<\/jats:italic>\n                    ) gene, which results in reduced deoxyhypusine synthase enzyme activity. Finally, DOHH (deoxyhypusine hydroxylase) disorder is an autosomal recessive disorder caused by bi\u2010allelic loss\u2010of\u2010function variants in the deoxyhypusine hydroxylase (\n                    <jats:italic>DOHH<\/jats:italic>\n                    ) gene, which causes decreased deoxyhypusine hydroxylase enzyme activity. Snyder\u2013Robinson syndrome was first described in 1969, while the other four syndromes have only been identified in the past 7\u2009years. A comprehensive phenotypic and genotypic description of these five syndromes is needed. We review the clinical and genetic features of these five polyaminopathies to create an inclusive clinical resource. A systematic keyword search strategy was used to identify all published cases in PubMed, Web of Science, and Scopus databases. The five known syndromes associated with the polyamine pathway share many similar clinical phenotypes, and yet patients with each syndrome present with distinctive syndromic features. This review will serve as a valuable resource for clinicians diagnosing and caring for patients with these rare polyaminopathies.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70029","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:13:48Z","timestamp":1766067228000},"page":"993-1003","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic and Phenotypic Features of the Five Known Polyaminopathies: A Critical Narrative Review"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-9248","authenticated-orcid":false,"given":"Elizabeth A.","family":"VanSickle","sequence":"first","affiliation":[{"name":"School of Nursing, Healthcare Genetics and Genomics Program Clemson University  Clemson South Carolina USA"},{"name":"Division of Medical Genetics Corewell Health\/Helen DeVos Children's Hospital  Grand Rapids Michigan USA"},{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Sarasua","sequence":"additional","affiliation":[{"name":"School of Nursing, Healthcare Genetics and Genomics Program Clemson University  Clemson South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-1405","authenticated-orcid":false,"given":"Tracy","family":"Lowe","sequence":"additional","affiliation":[{"name":"School of Nursing, Healthcare Genetics and Genomics Program Clemson University  Clemson South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Farrell","sequence":"additional","affiliation":[{"name":"School of Nursing, Healthcare Genetics and Genomics Program Clemson University  Clemson South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Boccuto","sequence":"additional","affiliation":[{"name":"School of Nursing, Healthcare Genetics and Genomics Program Clemson University  Clemson South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7770-1943","authenticated-orcid":false,"given":"Charles","family":"Schwartz","sequence":"additional","affiliation":[{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Department of Pediatrics and Human Development College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Pegg","sequence":"additional","affiliation":[{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Department of Cellular and Molecular Physiology Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine  Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-6548","authenticated-orcid":false,"given":"Angela","family":"Peron","sequence":"additional","affiliation":[{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Meyer Children's Hospital, IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Faundes","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Enfermedades Metab\u00f3licas Instituto de Nutrici\u00f3n y Tecnolog\u00eda de los Alimentos, Universidad de Chile  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mythily","family":"Ganapathi","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Cell Biology Columbia University Irving Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Boston Children's Hospital, Harvard Medical School  Boston Massachusetts USA"},{"name":"DHPS Foundation  Reston Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alban","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Hospital of Toulouse  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris","family":"Hofstede","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Prouteau","sequence":"additional","affiliation":[{"name":"Department of Genetics University Hospital of Angers  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Steindl","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Olson","sequence":"additional","affiliation":[{"name":"DHPS Foundation  Reston Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"DHPS Foundation  Reston Virginia USA"},{"name":"Department of Neurology NYU Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa L.","family":"Mastracci","sequence":"additional","affiliation":[{"name":"Department of Biology Indiana University\u2010Indianapolis  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Robert A.","family":"Casero","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy Murray","family":"Stewart","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-860X","authenticated-orcid":false,"given":"Susan","family":"Gilmour","sequence":"additional","affiliation":[{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Lankenau Institute for Medical Research  Wynnewood Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri","family":"Koerner","sequence":"additional","affiliation":[{"name":"The Snyder\u2010Robinson Foundation  McLean Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Jo","family":"Kutler","sequence":"additional","affiliation":[{"name":"The Snyder\u2010Robinson Foundation  McLean Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surender","family":"Rajasekaran","sequence":"additional","affiliation":[{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Department of Pediatrics and Human Development College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne","family":"Michael","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Corewell Health\/Helen DeVos Children's Hospital  Grand Rapids Michigan USA"},{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 S.","family":"Bachmann","sequence":"additional","affiliation":[{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Department of Pediatrics and Human Development College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb P.","family":"Bupp","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Corewell Health\/Helen DeVos Children's Hospital  Grand Rapids Michigan USA"},{"name":"International Center for Polyamine Disorders  Grand Rapids Michigan USA"},{"name":"Department of Pediatrics and Human Development College of Human Medicine, Michigan State University  Grand Rapids Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010015\u20109876\u2010y"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.15187"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010015\u20100235\u20108"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201006033\u20101"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096\u20108628(19960712)64:1"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.15687"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41073\u2010019\u20100064\u20108"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32641"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.06.334"},{"key":"e_1_2_12_11_1","first-page":"1993","volume-title":"GeneReviews [Internet]","author":"Bupp C.","year":"2022"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40523"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201072"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14643"},{"key":"e_1_2_12_15_1","unstructured":"Cremer K. S.Hoffjan A.Schmidt et\u00a0al.2020.Snyder\u2010Robinson Syndrome With Notable Intrafamilial Clinical Variability Detected By WES and PEDIA. 53rdEuropean Society of Human Genetics (ESHG) Conference."},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.056713"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.104097"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.24.00546"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021053\u20102"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2012.00162"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau1099"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.017"},{"key":"e_1_2_12_23_1","unstructured":"Halleb Y. M.Tessarech A.Ziegler et\u00a0al.2023.De Novo Splice Pathogenic Variant in the ODC1 Gene Causing Bachmann\u2010Bupp syndrome in a French Patient. 53rd European Society of Human Genetics (ESHG) Conference."},{"key":"e_1_2_12_24_1","unstructured":"Human Disease Genes ODC1.2024. Accessed November 15 2025.www.humandiseasegenes.nl\/odc1."},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008909"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048\u2010009\u20100184\u20102"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rare.2024.100025"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.103777"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rare.2023.100017"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci6010012"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a006122"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00476a050"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci11020029"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100361"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2004.11.001"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514122"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0925\u20104773(99)00064\u20107"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2023.100206"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726\u2010021\u201003023\u20106"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.TM118.003341"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.230"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.731661"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1982.243.5.C212"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17010077"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36116"},{"key":"e_1_2_12_46_1","unstructured":"PubChem Compound Summary for CID 3009.2024.Eflornithine. National Center for Biotechnology Information. Accessed October 1 2024.https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Eflornithine."},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010020\u201001095\u2010x"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67097"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2013.09.019"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100625.2010.01111.x"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.60677"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u201001096\u20104"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci9020044"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127246"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20190294"},{"key":"e_1_2_12_56_1","volume-title":"GeneReviews [Internet] 1993\u20102024","author":"Schwartz C. E.","year":"2013"},{"key":"e_1_2_12_57_1","volume-title":"Polyamines. Methods in Molecular Biology","author":"Schwartz C. E.","year":"2011"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1177\/000992286900801114"},{"key":"e_1_2_12_59_1","unstructured":"Snyder\u2010Robinson Foundation.2023.Medical Management of SRS. Accessed November 15 2025.www.snyder\u2010robinson.org\/medmanagement."},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523\u20101747.ep12340155"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.4322\/acr.2018.031"},{"issue":"6","key":"e_1_2_12_62_1","first-page":"374","article-title":"Unexplained Severe Multiple Disability and Epilepsy","volume":"84","author":"Steiner I.","year":"2013","journal-title":"Pediatric Practice"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198\u2010021\u201006228\u20103"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62473"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031327"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25126340"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010023\u201001373\u20100"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci10030038"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt229"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21310"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.06.010"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmga.70029","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmga.70029","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmga.70029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:45:13Z","timestamp":1787892313000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmga.70029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":70,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/ajmga.70029"],"URL":"https:\/\/doi.org\/10.1002\/ajmga.70029","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"assertion":[{"value":"2025-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}