{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T15:02:51Z","timestamp":1789570971304,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"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":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lethal congenital contracture syndrome 3 (LCCS3, MIM #611369) is a rare autosomal recessive neuromuscular disorder caused by biallelic loss\u2010of\u2010function (LOF) variants in\n                    <jats:italic>PIP5K1C<\/jats:italic>\n                    , reported in only two families to date. It typically presents with severe fetal akinesia, arthrogryposis multiplex congenita, and perinatal lethality due to respiratory insufficiency case. Herein, we report a new case with survival beyond birth. Prenatal findings included clubfeet with preserved amniotic fluid volume and fetal movements. The infant was delivered by cesarean section at 37\u2009+\u20097\u2009weeks following breech presentation and developed respiratory distress requiring 14\u2009days of ventilatory support. Physical examination revealed bilateral talipes equinovarus, flexion contractures of the knees, restricted hip mobility, clenched hands with flexion contractures of the third and fourth fingers, and hyperextension of the second and fifth fingers. Neurologically, he had encephalopathy, profound hypotonia with a frog posture, and abnormal neonatal reflexes with a discontinuous background pattern on cerebral function monitoring. Additional observed features were bilateral optic atrophy and hyperinsulinemic hypoglycemia responsive to Diazoxide. Trio genome sequencing identified a homozygous pathogenic splice\u2010site variant in\n                    <jats:italic>PIP5K1C<\/jats:italic>\n                    (c.1127+1G&gt;A, NM_012398.3). The infant died at 6\u2009months from multisystemic failure. Further studies are warranted to elucidate the pathomechanisms underlying the\n                    <jats:italic>PIP5K1C<\/jats:italic>\n                    defect and its phenotypic consequences.\n                  <\/jats:p>","DOI":"10.1111\/cge.70231","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:10:19Z","timestamp":1789567819000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A New Case of Lethal Congenital Contracture Syndrome Type 3 With Hyperinsulinism and Optic Atrophy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6588-3287","authenticated-orcid":false,"given":"Tameemi","family":"Abdalla Moady","sequence":"first","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology  Haifa Israel"},{"name":"Genetics Institute, Rambam Health Care Center  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar Hulin","family":"Ma'ayan","sequence":"additional","affiliation":[{"name":"The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4209-7624","authenticated-orcid":false,"given":"Michal","family":"Cohen","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology  Haifa Israel"},{"name":"Pediatric Endocrinology and Diabetes Unit Rambam Health Care Center  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-810X","authenticated-orcid":false,"given":"Karin","family":"Weiss","sequence":"additional","affiliation":[{"name":"The Ruth and Bruce Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology  Haifa Israel"},{"name":"Genetics Institute, Rambam Health Care 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