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Recently,\n                    <jats:italic>de novo<\/jats:italic>\n                    heterozygous missense variants in the N\u2010terminal regulatory domain of\n                    <jats:italic>HK1<\/jats:italic>\n                    have been associated with neurodevelopmental disorders with visual defects and brain anomalies (NEDVIBA), likely through gain\u2010of\u2010function mechanisms causing excessive glucose phosphorylation. Tuberous sclerosis complex (TSC), a neurocutaneous syndrome characterized by hamartoma formation in multiple organs, results from TSC1\/TSC2 complex dysfunction and mTOR pathway dysregulation. To date, no association between NEDVIBA and TSC has been reported. Here, we present a 4\u2010year\u2010old boy with developmental delay meeting clinical diagnostic criteria for TSC, including hypopigmented skin patches and radial migration lines on brain MRI. Genetic analysis revealed the recurrent\n                    <jats:italic>de novo HK1<\/jats:italic>\n                    variant c.1334C&gt;T (p.Ser445Leu) associated with NEDVIBA, while no pathogenic variants in\n                    <jats:italic>TSC1<\/jats:italic>\n                    \/\n                    <jats:italic>TSC2<\/jats:italic>\n                    were detected. Notably, our patient lacked hamartomas, a hallmark of TSC. This case expands the phenotypic spectrum of NEDVIBA and suggests that\n                    <jats:italic>HK1<\/jats:italic>\n                    variants should be considered in the differential diagnosis of TSC\u2010like presentations, particularly in cases without hamartomas or identifiable\n                    <jats:italic>TSC1<\/jats:italic>\n                    \/\n                    <jats:italic>TSC2<\/jats:italic>\n                    variants.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64156","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T06:04:25Z","timestamp":1750226665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A\n                    <i>\n                      de novo\n                      <scp>HK1<\/scp>\n                    <\/i>\n                    Variant in a Boy Fulfilling the Diagnostic Criteria for Tuberous Sclerosis Complex: Expanding the Phenotypic Spectrum of\n                    <scp>NEDVIBA<\/scp>"],"prefix":"10.1002","volume":"197","author":[{"given":"Daisuke","family":"Ariyasu","sequence":"first","affiliation":[{"name":"Department of Pediatrics Kawasaki Municipal Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Radiology Eiju General Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kawasaki Municipal Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Saito","sequence":"additional","affiliation":[{"name":"Hagukumi Mother and Child Clinic  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moeko","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics NHO Tokyo Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4248-0033","authenticated-orcid":false,"given":"Kaoru","family":"Fujinami","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics NHO Tokyo Medical Center  Tokyo Japan"},{"name":"Laboratory of Visual Physiology Division of Vision Research, National Institute of Sensory Organs, NHO Tokyo Medical Center  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takatoshi","family":"Tsuchihashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kawasaki Municipal Hospital  Kanagawa Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-2759","authenticated-orcid":false,"given":"Kazuki","family":"Yamazawa","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics NHO Tokyo Medical Center  Tokyo 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