{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:30:16Z","timestamp":1790220616404,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T00:00:00Z","timestamp":1725321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Alkuraya\u2010Ku\u010dinskas syndrome (AKS) is an autosomal recessive multisystem disorder resulting from mutations in the\n                      <jats:italic>BLTP1<\/jats:italic>\n                      gene, formerly known as\n                      <jats:italic>KIAA1109<\/jats:italic>\n                      . Primary manifestations include brain malformations, arthrogryposis, and clubfeet. Cardiac, renal, and ophthalmologic abnormalities may also be observed, while nonimmune hydrops is rare. We present a case of two novel\n                      <jats:italic>BLTP1<\/jats:italic>\n                      canonical splice\u2010site variants in a fetus with multiple congenital anomalies, including hydrops, a kinked brainstem, and joint contractures. A systematic literature review was conducted to describe the prenatal phenotype of AKS, which was inspired by our case. Our systematic literature review of the prenatal phenotype in 19 cases, including our additional case, demonstrated joint contractures in 90% (18\/20), ventriculomegaly in 60% (12\/20), brainstem dysgenesis in 50% (10\/20), cerebellar hypoplasia in 50% (10\/20), parenchymal thinning with lissencephalic aspect in 60% (12\/20), and facial dysmorphism in 70% (14\/20) of reported AKS cases. In addition to our case, hydrops was reported in two other families. AKS should be considered in fetal presentations with characteristic features, especially brainstem kinking and joint contractures. Exome sequencing, including coverage of canonical intronic splice\u2010site variants, can clarify the diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      registration: NCT03911531\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.6637","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:26:12Z","timestamp":1725409572000},"page":"1381-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prenatal Phenotype of Alkuraya\u2010Ku\u010dinskas Syndrome: A\u00a0Novel Case and Systematic Literature Review"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7323-7629","authenticated-orcid":false,"given":"Stephanie M.","family":"Rice","sequence":"first","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine Department of Obstetrics and Gynecology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-2331","authenticated-orcid":false,"given":"Dante F.","family":"Varotsis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Sidney Kimmel Medical College at Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-383X","authenticated-orcid":false,"given":"Sascha","family":"Wodoslawsky","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College at Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4433-7014","authenticated-orcid":false,"given":"Elizabeth","family":"Critchlow","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Medical College at Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3449-3862","authenticated-orcid":false,"given":"Ruby","family":"Liu","sequence":"additional","affiliation":[{"name":"Revvity Omics, Inc.  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5013-3456","authenticated-orcid":false,"suffix":"Jr.","given":"Rodney A.","family":"McLaren","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine Department of Obstetrics and Gynecology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-8487","authenticated-orcid":false,"given":"Mona M.","family":"Makhamreh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Maimonides Medical Center  Brooklyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3512-8672","authenticated-orcid":false,"given":"Brandy","family":"Firman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Sidney Kimmel Medical College at Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-4302","authenticated-orcid":false,"given":"Seth I.","family":"Berger","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research at Children's National Hospital  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-0333","authenticated-orcid":false,"given":"Huda B.","family":"Al\u2010Kouatly","sequence":"additional","affiliation":[{"name":"Division of Maternal\u2010Fetal Medicine Department of Obstetrics and Gynecology Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.806752"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010020\u201001074\u20102"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5589"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.12.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13448"},{"key":"e_1_2_11_7_1","unstructured":"Online Mendelian Inheritance in Man (OMIM). (2024). OMIM entry 611565.https:\/\/www.omim.org\/entry\/611565."},{"key":"e_1_2_11_8_1","unstructured":"HUGO Gene Nomenclature Committee (HGNC). (2024). BLTP1 (HGNC ID: 26953).https:\/\/www.genenames.org\/data\/gene\u2010symbol\u2010report\/#!\/hgnc_id\/26953."},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104427"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2018.12.004"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13353\u2010018\u20100444\u20107"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.5654.2"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.111"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.08.017"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.017"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001121\u20100"},{"key":"e_1_2_11_17_1","unstructured":"National Center for Biotechnology Information (NCBI). (2024). NG_015813.3 Homo sapiens [BLTP1] gene complete sequence.https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/NG_015813.3."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.12.018"},{"key":"e_1_2_11_19_1","unstructured":"Genome Aggregation Database (gnomAD). (2024). BLTP1 gene c.4916+2T>C and c.10671\u20101G>C variants gnomAD v[4.0.0].https:\/\/gnomad.broadinstitute.org\/variant\/4\u2010122244029\u2010T\u2010C?dataset=gnomad_r4andhttps:\/\/gnomad.broadinstitute.org\/variant\/4\u2010122318146\u2010G\u2010C?dataset=gnomad_r4."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.015"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13472"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-2-69"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu082"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.12.007"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2015.05.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00967-0"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6637","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T10:38:52Z","timestamp":1728902332000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,3]]},"references-count":26,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/pd.6637"],"URL":"https:\/\/doi.org\/10.1002\/pd.6637","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,3]]},"assertion":[{"value":"2024-04-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}