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Malformations also included agenesis of the corpus callosum, abnormal cortical gyres, dilation of the aqueduct, bilateral endolymphatic sac, bilateral cystic cocci\u2010vestibular malformation, and a cribriform defect. The 3D TC craniofacial images showed abnormal frontonasal transition region, with a bone bifurcation, and partial agenesis of nasal bone. The trunk and upper and lower limbs were normal. To our knowledge, this rare association of holoprocensephaly with frontonaso\u2010orbital encephaloceles without limb anomalies has never been reported before. Karyotype was normal. SNP\u2010array showed no copy\u2010number alterations but revealed 25% of regions of homozygosity (ROH) with normal copy number, indicating a high coefficient of inbreeding, which significantly increases the risk for an autosomal recessive disorder. Whole exome sequencing analysis did not reveal any pathogenic or likely pathogenic variants. We discuss the possible influence of two variants of uncertain significance found within the patient's ROHs. First, a missense p.(Gly394Ser) in <jats:italic>PCSK9<\/jats:italic>, a gene involved in the regulation of plasma low\u2010density lipoprotein cholesterol. Second, an inframe duplication p.(Ala75_Ala81dup) in <jats:italic>SP8<\/jats:italic>, a zinc\u2010finger transcription factor that regulates signaling centers during craniofacial development. Further studies and\/or the identification of other patients with a similar phenotype will help elucidate the genetic etiology of this complex case.<\/jats:p>","DOI":"10.1002\/ajmg.a.61305","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T06:35:28Z","timestamp":1564382128000},"page":"2170-2177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Holoprosencephaly, orofacial cleft, and frontonaso\u2010orbital encephaloceles: Genetic evaluation of a possible new syndrome"],"prefix":"10.1002","volume":"179","author":[{"given":"Antonio","family":"Richieri\u2010Costa","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Hospital for Rehabilitation of Craniofacial Anomalies (HRCA) University of S\u00e3o Paulo  Bauru S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4526-3336","authenticated-orcid":false,"given":"Roseli M.","family":"Zechi\u2010Ceide","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Hospital for Rehabilitation of Craniofacial Anomalies (HRCA) University of S\u00e3o Paulo  Bauru S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosana M.","family":"Candido\u2010Souza","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Hospital for Rehabilitation of Craniofacial Anomalies (HRCA) University of S\u00e3o Paulo  Bauru S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rejane A. 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