Case report
Unique phenotype in a patient with CHARGE syndrome
1 State University of New York Downstate Medical Center, Children's Hospital at Downstate, Department of Pediatrics, Division of Pediatric Endocrinology, Brooklyn, NY 11203 USA
2 Institute of Molecular Medicine and Genetics, The Medical College of Georgia, Section of Reproductive Endocrinology, Infertility, and Genetics, Department of Obstetrics and Gynecology, Augusta, GA 30912, USA
3 State University of New York Downstate Medical Center, Department of Pathology, Division of Molecular Pathology, Brooklyn, NY 11203, USA
4 Institute of Nanotechnology, Karlsruhe Institute of Technology, PO Box 3640. 76021 Karlsruhe, Germany
5 Institute of Human Genetics, University Hospital Jena Kollegiengasse 1007743 Jena, Germany
6 State University of New York Downstate Medical Center, Children's Hospital at Downstate, Department of Pediatrics, Division of Pediatric Nephrology, Brooklyn, NY 11203 USA
International Journal of Pediatric Endocrinology 2011, 2011:11 doi:10.1186/1687-9856-2011-11
Published: 13 October 2011Abstract
CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the first CHARGE subject reported with bilateral multicystic dysplastic kidneys. Furthermore, with structural modeling and murine expression studies, we characterize a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights that stringent fulfillment of conventional criteria should not strictly guide genetic analysis.
