{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:45:03Z","timestamp":1790858703367,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:p>Whole\u2010exome sequencing has established <jats:italic>IQSEC2<\/jats:italic> as a neurodevelopmental disability gene. The <jats:italic>IQSEC2<\/jats:italic> variant phenotype includes developmental delay, intellectual disability, epilepsy, hypotonia, autism, developmental regression, microcephaly and stereotypies but is yet to be fully described. Presented here are 14 new patients with <jats:italic>IQSEC2<\/jats:italic> variants. In addition to the established features, we observed: gait ataxia in 7 of 9 (77.8%), drooling in 9 of 14 (64.2%), early feeding difficulties in 7 of 14 (50%), structural brain abnormalities in 6 of 13 (46.2%), brachycephaly in 5 of 14 (35.7%), and scoliosis and paroxysms of laughter each in 4 of 14 (28.6%). We suggest that these are features of the <jats:italic>IQSEC2<\/jats:italic>\u2010related disorder. Gastrostomy requirement, plagiocephaly, strabismus and cortical blindness, each seen in 2 of 14 (14.3%), may also be associated. Shared facial features were noted in 8 of 14 patients, and shared hair patterning was identified in 5 of 14 patients.<\/jats:p><jats:p>This study further delineates the <jats:italic>IQSEC2<\/jats:italic> phenotypic spectrum and supports the notion of an emerging <jats:italic>IQSEC2<\/jats:italic> syndrome. We draw parallels between the <jats:italic>IQSEC2<\/jats:italic>\u2010related disorder and the Angelman\u2010\/Rett\u2010\/Pitt\u2010Hopkins syndrome group of conditions and recommend the addition of <jats:italic>IQSEC2<\/jats:italic> to epilepsy and developmental delay gene panels. We observed discordant phenotypes in monozygotic twins and apparent gonadal mosaicism, which has implications for recurrence risk counselling in the <jats:italic>IQSEC2<\/jats:italic>\u2010related disorder.<\/jats:p>","DOI":"10.1111\/cge.13507","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T06:04:44Z","timestamp":1548137084000},"page":"496-506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Deep phenotyping of 14 new patients with <i>IQSEC2<\/i> variants, including monozygotic twins of discordant phenotype"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0776-0091","authenticated-orcid":false,"given":"Jessica A.","family":"Radley","sequence":"first","affiliation":[{"name":"West Midlands Regional Clinical Genetics Service and Birmingham Health Partners Birmingham Women's and Children's Hospitals NHS Foundation Trust  Birmingham 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