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No variant assessed to be pathogenic or likely pathogenic was detected in the<jats:italic>GLI3<\/jats:italic>gene in either child. This syndrome appears to be distinct from the inherited Pallister\u2013Hall syndrome associated with<jats:italic>GLI3<\/jats:italic>variants, which is characterized by hypothalamic hamartoma, mesoaxial polydactyly, and other anomalies. In the individuals described here, manifestations outside of the central nervous system were milder and the mesoaxial polydactyly, which is common in individuals with Pallister\u2013Hall syndrome, was absent. Instead, these children had multiple buccolingual frenula together with the unusual appearance of the fifth digit. It remains unclear whether these two individuals represent a separate nosologic entity or if they represent a milder manifestation of one of the more severe syndromes associated with a hypothalamic hamartoma.<\/jats:p>","DOI":"10.1002\/ajmg.a.63306","type":"journal-article","created":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T10:24:46Z","timestamp":1689157486000},"page":"2337-2343","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and molecular heterogeneity of syndromic hypothalamic hamartoma"],"prefix":"10.1002","volume":"191","author":[{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"first","affiliation":[{"name":"Pediatric Neurology, The Neurology Service Massachusetts General Hospital Boston Massachusetts United States"},{"name":"Division of Neurology The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States"},{"name":"Sidney Kimmel Medical College Philadelphia Pennsylvania United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalpathy S.","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, The Neurology Service Massachusetts General Hospital Boston Massachusetts United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer J.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Center for Precision Health Research, National Human Genome Research Institute National Institutes of Health Bethesda Maryland United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Mass General for Children Boston Massachusetts United States"},{"name":"Nemours Children's Health, DV Wilmington Delaware United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren J.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Medical Genetics and Metabolism Unit Mass General for Children Boston Massachusetts United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0197-3811","authenticated-orcid":false,"given":"Leslie G.","family":"Biesecker","sequence":"additional","affiliation":[{"name":"Center for Precision Health Research, National Human Genome Research Institute National Institutes of Health Bethesda Maryland United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-4848","authenticated-orcid":false,"given":"Lewis B.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Medical Genetics and Metabolism Unit Mass General for Children Boston Massachusetts United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1684\/j.1950-6945.2003.tb00017.x","article-title":"Heritable syndromes with hypothalamic hamartoma and seizures: Using rare syndromes to understand more common disorders","volume":"5","author":"Biesecker L. 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