Expanding phenotype with severe midline brain anomalies and missense variant supports a causal role for FOXA2 in 20p11.2 deletion syndrome |
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| Authors: | Jennifer N. Dines Yajuan J. Liu Whitney Neufeld‐Kaiser Taylor Sawyer Gisele E. Ishak Hannah M. Tully Melissa Racobaldo Amarilis Sanchez‐Valle Christine M. Disteche Jane Juusola Erin Torti Kirsty McWalter Katrina M. Dipple |
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| Affiliation: | 1. Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington;2. Department of Pediatrics, Division of Genetic Medicine, University of Washington/Seattle Children's Hospital, Seattle, Washington;3. Department of Pathology, University of Washington School of Medicine, Seattle, Washington;4. Department of Pediatrics, Division of Neonatology, University of Washington, Seattle, Washington;5. Department of Radiology, University of Washington, Seattle Children's Hospital, Seattle, Washington;6. Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington;7. Division of Pediatric Neurology, Seattle Children's Hospital, Seattle, Washington;8. Division of Genetics and Metabolism, University of South Florida, Tampa, Florida;9. GeneDx, Inc., Gaithersburg, Maryland;10. Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WashingtonCo‐senior authors. Katrina M. Dipple, Seattle Children's Research Institute, OC.9.850—Medical Genetics, 4800 Sand Point Way NE, Seattle, WA 98105. |
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| Abstract: | Rare individuals with 20p11.2 proximal deletions have been previously reported, with a variable phenotype that includes heterotaxy, biliary atresia, midline brain defects associated with panhypopituitarism, intellectual disability, scoliosis, and seizures. Deletions have ranged in size from 277 kb to 11.96 Mb. We describe a newborn with a de novo 2.7 Mb deletion of 20p11.22p11.21 that partially overlaps previously reported deletions and encompasses FOXA2. Her clinical findings further expand the 20p11.2 deletion phenotype to include severe midline cranial and intracranial defects such as aqueductal stenosis with hydrocephalus, mesencephalosynapsis with diencephalic‐mesencephalic junction dysplasia, and pyriform aperture stenosis. We also report one individual with a missense variant in FOXA2 who had abnormal glucose homeostasis, panhypopituitarism, and endodermal organ dysfunction. Together, these findings support the critical role of FOXA2 in panhypopituitarism and midline defects. |
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| Keywords: | 20p proximal deletion heterotaxy hydrocephalus mesencephalosynapsis with diencephalic‐mesencephalic junction dysplasia panhypopituitarism |
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