{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:55:33Z","timestamp":1791082533338,"version":"4.1.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"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. Pediatr."],"abstract":"<jats:p>\n                    Polyaminopathies are a family of rare genetic developmental disorders caused by pathogenic variants in genes involved in polyamine homeostasis and metabolism, and related biological pathways, including the hypusine biosynthesis pathway. DOHH is the enzyme catalyzing the last step of hypusine biosynthesis.\n                    <jats:italic>DOHH<\/jats:italic>\n                    -related disorders, caused by biallelic variants in the\n                    <jats:italic>DOHH<\/jats:italic>\n                    gene, were first described in 2022 in five patients exhibiting severe neurodevelopmental delay, congenital heart defects, and growth restriction. We report on a 10-year-old boy, the first child of consanguineous parents, whose clinical presentation began prenatally with increased nuchal translucency (7.5\u2005mm), pericardial effusion and thickening of the right ventricular anterior wall. Postnatally, he developed dilated cardiomyopathy with left ventricular hypertrabeculation and hypoparathyroidism. Follow-up revealed delays in motor and cognitive milestones. Trio exome sequencing (ES) identified an inherited homozygous c.455C&amp;gt;T (p.Pro152Leu) pathogenic variant in\n                    <jats:italic>DOHH<\/jats:italic>\n                    . Review of the literature shows that our patient exhibits milder neurodevelopmental impairment and intellectual disability than previously described, and no growth restriction. Interestingly, this is the second report of increased prenatal nuchal translucency in\n                    <jats:italic>DOHH<\/jats:italic>\n                    -related disorders. As cardiomyopathy and hypoparathyroidism are being reported for the first time in this condition, additional cases are needed to corroborate or disprove this association. This case expands the phenotypic spectrum of\n                    <jats:italic>DOHH<\/jats:italic>\n                    -related disorders. It supports the diagnostic utility of exome sequencing in rare diseases, and highlights the importance of systematic bioinformatic reanalysis, long-term follow-up for accurate phenotypic characterization, and genetic counseling.\n                  <\/jats:p>","DOI":"10.3389\/fped.2026.1733592","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:41:58Z","timestamp":1780551718000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: A new patient expanding the clinical spectrum of DOHH-associated syndrome with increased nuchal translucency, cardiomyopathy, hypoparathyroidism and mild intellectual disability"],"prefix":"10.3389","volume":"14","author":[{"given":"Elise","family":"Daire","sequence":"first","affiliation":[{"name":"Pediatric Cardiology Department, Amiens University Hospital","place":["Amiens, France"]},{"name":"EA4666 Hematim, University of Picardie\u2013Jules Verne","place":["Amiens, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Dirani","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Department, Amiens University Hospital","place":["Amiens, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amiens University Hospital","place":["Amiens, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Segolene","family":"Delmas Lanta","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynaecology and Reproductive Medicine, Amiens University Hospital","place":["Amiens, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Cav\u00e9","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique du D\u00e9veloppement, H\u00f4pital Robert Debr\u00e9, AP-HP","place":["Paris, France"]},{"name":"Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline Alice","family":"Bonnard","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique du D\u00e9veloppement, H\u00f4pital Robert Debr\u00e9, AP-HP","place":["Paris, France"]},{"name":"Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedicte","family":"Demeer","sequence":"additional","affiliation":[{"name":"Genetic Department, CLAD, Amiens University Hospital","place":["Amiens, France"]},{"name":"Chimere INSERM UA21, University of Picardie-Jules Verne, Institut Faire Face","place":["Amiens, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s00726-021-03023-6","article-title":"Post-translational formation of hypusine in eIF5A: implications in human neurodevelopment","volume":"54","author":"Park","year":"2022","journal-title":"Amino Acids"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmga.70029","article-title":"Genetic and phenotypic features of the five known polyaminopathies: a critical narrative review","author":"VanSickle","year":"2025","journal-title":"Am J Med Genet A"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/j.ajhg.2022.06.010","article-title":"Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder","volume":"109","author":"Ziegler","year":"2022","journal-title":"Am J Hum 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