Natural History and Genotype-Phenotype Correlations in 72 Individuals with SATB2-Associated Syndrome

Authors

Yuri A Zarate, University of Arkansas for Medical Sciences
Constance L Smith-Hicks, Kennedy Krieger Institute and Johns Hopkins University School of Medicine
Carol Greene, University of Maryland Baltimore
Mary-Alice Abbott, Baystate Medical Center
Victoria M Siu, Western University
Amy R U L Calhoun, University of Iowa
Arti Pandya, University of North Carolina at Chapel Hill
Chumei Li, McMaster University Medical Center
Elizabeth A Sellars, University of Arkansas for Medical Sciences
Julie Kaylor, InformedDNA
Katherine Bosanko, University of Arkansas for Medical Sciences
Louisa Kalsner, Connecticut Children's Medical Center and University of Connecticut Health Center
Alice Basinger, Cook Children's Physician Network
Anne M Slavotinek, University of California San Francisco
Hazel Perry, University of California San Francisco
Margarita Saenz, Children's Hospital Colorado
Marta Szybowska, McMaster University Medical Center
Louise C Wilson, Great Ormond Street for Children NHS Foundation Trust
Ajith Kumar, Great Ormond Street for Children NHS Foundation Trust
Caroline Brain, Great Ormond Street for Children NHS Foundation Trust
Meena Balasubramanian, Sheffield Children's NHS Foundation Trust
Holly Dubbs, Children's Hospital of Philadelphia
Xilma R Ortiz-Gonzalez, Children's Hospital of Philadelphia
Elaine Zackai, Children's Hospital of Philadelphia
Quinn Stein, Sanford Children's Hospital
Cynthia M Powell, University of North Carolina at Chapel Hill
Samantha Schrier Vergano, Children's Hospital of The King's Daughters
Allison Britt, University of Texas Medical Branch
Angela Sun, University of Washington
Wendy Smith, The Barbara Bush Children's Hospital
E Martina Bebin, University of Alabama at Birmingham
Jonathan Picker, Boston Children's Hospital
Amelia Kirby, SSM Health Cardinal Glennon Children's Hospital
Hailey Pinz, SSM Health Cardinal Glennon Children's Hospital
Hannah Bombei, University of Iowa
Sonal Mahida, Johns Hopkins University School of Medicine
Julie S Cohen, Johns Hopkins University School of Medicine
Ali Fatemi, Johns Hopkins University School of Medicine
Hilary J Vernon, Johns Hopkins University School of Medicine
Rebecca McClellan, Johns Hopkins University School of Medicine
Leah R Fleming, St. Luke's Children's Hospital
Brittney Knyszek, St. Luke's Children's Hospital
Michelle Steinraths, University of British Columbia
Cruz Velasco Gonzalez, University of Arkansas for Medical Sciences
Anita E Beck, Seattle Children's Hospital, Seattle
Katie L Golden-Grant, Seattle Children's Hospital, Seattle
Alena Egense, University of Maryland Baltimore
Aditi Parikh, University of Toledo Department of Pediatrics
Chantalle Raimondi, Advocate Children's Hospital
Brad Angle, Advocate Children's Hospital
William Allen, Fullerton Genetics Center
Suzanna Schott, Fullerton Genetics Center
Adi Algrabli, FDNA, Inc
Nathaniel H Robin, University of Alabama at Birmingham
Joseph W Ray, University of Texas Medical Branch
David B Everman, Greenwood Genetic Center
Michael J Gambello, Emory University School of Medicine
Wendy K Chung, Columbia University

Document Type

Article

Publication Date

4-2018

Journal

American Journal of Medical Genetics

Volume

176

Issue

4

First Page

925

Last Page

935

URL with Digital Object Identifier

https://doi.org/10.1002/ajmg.a.38630

Abstract

SATB2-associated syndrome (SAS) is an autosomal dominant disorder characterized by significant neurodevelopmental disabilities with limited to absent speech, behavioral issues, and craniofacial anomalies. Previous studies have largely been restricted to case reports and small series without in-depth phenotypic characterization or genotype-phenotype correlations. Seventy two study participants were identified as part of the SAS clinical registry. Individuals with a molecularly confirmed diagnosis of SAS were referred after clinical diagnostic testing. In this series we present the most comprehensive phenotypic and genotypic characterization of SAS to date, including prevalence of each clinical feature, neurodevelopmental milestones, and when available, patient management. We confirm that the most distinctive features are neurodevelopmental delay with invariably severely limited speech, abnormalities of the palate (cleft or high-arched), dental anomalies (crowding, macrodontia, abnormal shape), and behavioral issues with or without bone or brain anomalies. This comprehensive clinical characterization will help clinicians with the diagnosis, counseling and management of SAS and help provide families with anticipatory guidance.