{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:49:22Z","timestamp":1782362962758,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, the genetic cause of HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) was identified as biallelic pathogenic variants in <jats:italic>P4HTM<\/jats:italic>, which encodes an atypical member of the prolyl 4\u2010hydroxylases (P4Hs) family of enzymes. We report seven patients from four new families in whom HIDEA was only diagnosed after whole\u2010exome sequencing (WES) revealed novel disease\u2010causing variants in <jats:italic>P4HTM<\/jats:italic>. We note the variable phenotypic expressivity of the syndrome except for cognitive impairment\/developmental delay, and hypotonia, which seem to be consistent findings. One patient only presented with hypotonia, developmental delay, and abnormal eye movements, which highlights the challenge in diagnosing milder cases with this new syndrome. Other notable features include mild facial dysmorphism, obesity, and brain dysmyelination and atrophy. We conclude that HIDEA is a highly variable syndrome and suspect that a large fraction of patients will be diagnosed via reverse phenotyping after recessive <jats:italic>P4HTM<\/jats:italic> variants are identified by agnostic genomic sequencing assays.<\/jats:p>","DOI":"10.1002\/ajmg.a.61885","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T09:55:44Z","timestamp":1600854944000},"page":"2999-3006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Further delineation of <scp>HIDEA<\/scp> syndrome"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2999-2229","authenticated-orcid":false,"given":"Sateesh","family":"Maddirevula","sequence":"first","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Center  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-930X","authenticated-orcid":false,"given":"Tawfeg","family":"Ben\u2010Omran","sequence":"additional","affiliation":[{"name":"Division of Genetic and Genomic Medicine,Sidra Medicine. 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Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard\u2010Health Affairs (MNGHA)  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisham","family":"Alkuraya","sequence":"additional","affiliation":[{"name":"Global Eye Care Specialized Medical Center Hospital  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alfaifi","sequence":"additional","affiliation":[{"name":"Pediatrics Department Security Forces Hospital  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Hamed","family":"Alfalah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jouf University  Sakaka Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-5237","authenticated-orcid":false,"given":"Hessa 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