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The disorder has been associated with biallelic pathogenic variants in the patatin\u2010like phospholipase domain\u2010containing protein 6 (<jats:italic>PNPLA6)<\/jats:italic> gene. We present an individual with a clinical diagnosis consistent with BNHS who lacked any <jats:italic>PNPLA6<\/jats:italic> variants but on quartet family exome sequencing had a de novo variant in the hexokinase 1 (<jats:italic>HK1<\/jats:italic>) gene (NM_000188.2 [GRCh37\/hg19]: g.71139826G&gt;A, c.1240G&gt;A, p.Gly414Arg), suggesting genetic heterogeneity for BNHS. Longitudinal follow\u2010up indicated neurological deterioration, neuropsychiatric symptoms, and progressive cerebellar atrophy. The BNHS phenotype overlaps and expands the known <jats:italic>HK1<\/jats:italic> genotypic and phenotypic spectrum. Individuals with variants in <jats:italic>HK1<\/jats:italic> should undergo evaluation for hypogonadotropic hypogonadism, potentially amenable to treatment.<\/jats:p>","DOI":"10.1002\/ajmg.a.63045","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T12:51:03Z","timestamp":1671627063000},"page":"624-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A de novo hexokinase 1 (<scp><i>HK1<\/i><\/scp>) variant presenting as <scp>Boucher\u2013Neuh\u00e4user<\/scp> syndrome"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7570-1018","authenticated-orcid":false,"given":"Ryan H.","family":"Peretz","sequence":"first","affiliation":[{"name":"Undiagnosed Diseases Program National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih 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