title: Setleis syndrome due to inheritance of the 1p36.22p36.21 duplication: evidence for lack of penetrance.
abstract: Setleis syndrome, focal facial dermal dysplasia type III (FFDD3, MIM #227260), is characterized by scar-like bitemporal lesions and other ocular and facial dysmorphic features. The syndrome results from recessive mutations in the TWIST2 gene, encoding a basic helix-loop-helix transcription factor or de novo genomic duplication or triplication, which include 1.3 Mb at 1p36.22p36.21, or other yet undefined lesions, emphasizing the syndrome's genetic heterogeneity. Recently, three patients were reported with 1p36.22p36.21 duplications/triplication that had the characteristic FFDD3 features and developmental delay or intellectual disabilities. Here, we describe a male with this microduplication, and the typical FFDD3 phenotype, but normal intelligence. Notably, his duplication was inherited from his father who did not have any FFDD3 manifestations, indicating lack of penetrance of the 1p36.22p36.21 microduplication. These findings emphasize phenotypic heterogeneity of the 1p36.22p36.21 copy number variant and the importance of screening the parents of patients with the 1p36.22p36.21 copy number variant to determine whether the duplication/triplication is de novo or inherited, for informed reproductive and genetic counseling.
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors: Beom Hee
authors: BH
authors: Lee
authors: Department of Dermatology, Birmingham Children's Hospital, National Health Service Foundation Trust, Birmingham, UK.
authors: Christos
authors: C
authors: Kasparis
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Brenden
authors: B
authors: Chen
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Hui
authors: H
authors: Mei
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Lisa
authors: L
authors: Edelmann
authors: Department of Dermatology, Birmingham Children's Hospital, National Health Service Foundation Trust, Birmingham, UK.
authors: Celia
authors: C
authors: Moss
authors: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: David D
authors: DD
authors: Weaver
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Robert J
authors: RJ
authors: Desnick
mesh_terms: D058674:Chromosome Duplication / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004476:Ectodermal Dysplasia; D005260:Female; D005489:Focal Dermal Hypoplasia / Q000235:genetics* / Q000473:pathology; D000090303:Focal Facial Dermal Dysplasias; D006801:Humans; D008297:Male; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology; D051879:Twist-Related Protein 1 / Q000235:genetics; D055815:Young Adult
chemical_list: D012097:Repressor Proteins; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1