title: Expanding the SPECC1L mutation phenotypic spectrum to include Teebi hypertelorism syndrome.
abstract: Teebi hypertelorism syndrome is a rare autosomal dominant disorder that has eluded a molecular etiology since first described in 1987. Here we report on two unrelated families with a Teebi hypertelorism-like syndrome and Teebi hypertelorism phenotype who have missense mutations in Sperm Antigen With Calponin Homology And Coiled-Coil Domains (SPECC1L), previously associated with oblique facial clefting and Opitz G/BBB syndrome. The first patient and his affected mother were previously-reported by Hoffman et al. in this journal as a new syndrome resembling Teebi hypertelorism and Aarskog syndromes in 2007. This patient had hypertelorism, sagittal and coronal craniosynostosis, ptosis, natal teeth, unusual umbilicus, shawl scrotum, small hands, and feet, with grossly normal development. Our second patient had classic Teebi hypertelorism syndrome with hypertelorism and a giant umbilical hernia. Patient one and his affected mother had a c.1260G>C:p.E420D variant and patient two had a de novo c.1198_1203delATACAC:p.I400_H401del variant in SPECC1L. We review the phenotypic findings in the previously-published Teebi hypertelorism syndrome patients, and the Opitz G/BBB patients with SPECC1L mutations. In addition we emphasize the findings of aortic root dilation and craniosynostosis in these patients, which should be considered in their management.
authors.affiliation: Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Bhoj
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Harr
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Tian
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Haijun
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.affiliation: Division of Genetics, Department of Pediatrics, Boston Medical Center, Boston, Massachusetts.
authors.forename: Jodi D
authors.initials: JD
authors.lastname: Hoffman
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Department of Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
mesh_terms: D000015:Abnormalities, Multiple; D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities; D004252:DNA Mutational Analysis; D019066:Facies; D005190:Family; D005532:Foot Deformities, Congenital; D006228:Hand Deformities, Congenital; D006801:Humans; D006972:Hypertelorism / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics*; D000096985:Calponins; D004947:Esophagus / Q000002:abnormalities; D007021:Hypospadias
chemical_list: D010750:Phosphoproteins; C558855:SPECC1L protein, human; D000096985:Calponins
keywords: Opitz G/BBB syndrome; craniosynostosis hoffman type; hypertelorism; sperm antigen with calponin homology and coiled-coil domains; teebi hypertelorism syndrome