Expanding the reproductive organ phenotype of CHD7-spectrum disorder

Authors

Tomoki T. Nomakuchi, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Melinda Danowitz, Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, USA.
Blythe Stewart, Human Genetics Unit, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
Jacqueline Leonard, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Kosuke Izumi, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Ian Krantz, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Thomas F. Kolon, Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
David Langdon, Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, USA.
Cara Skraban, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Jason Van Batavia, Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Elaine Zackai, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Kai Jiao, Center for Biotechnology & Genomic Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA.
Rebecca Linn, Division of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Caitlin Alexander, Division of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mark Zaontz, Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Maria G. Vogiatzi, Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, USA.
Louise C. Pyle, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Document Type

Journal Article

Publication Date

2-16-2023

Journal

American journal of medical genetics. Part A

DOI

10.1002/ajmg.a.63148

Keywords

CHARGE; CHD7; DSD; Kallmann syndrome

Abstract

CHD7 disorder is a multiple congenital anomaly syndrome with a highly variable phenotypic spectrum, and includes CHARGE syndrome. Internal and external genital phenotypes frequently seen in CHD7 disorder include cryptorchidism and micropenis in males, and vaginal hypoplasia in females, both thought to be secondary to hypogonadotropic hypogonadism. Here, we report 14 deeply phenotyped individuals with known CHD7 variants (9 pathogenic/likely pathogenic and 5 VOUS) and a range of reproductive and endocrine phenotypes. Reproductive organ anomalies were observed in 8 of 14 individuals and were more commonly noted in males (7/7), most of whom presented with micropenis and/or cryptorchidism. Kallmann syndrome was commonly observed among adolescents and adults with CHD7 variants. Remarkably, one 46,XY individual presented with ambiguous genitalia, cryptorchidism with Müllerian structures including uterus, vagina and fallopian tubes, and one 46,XX female patient presented with absent vagina, uterus and ovaries. These cases expand the genital and reproductive phenotype of CHD7 disorder to include two individuals with genital/gonadal atypia (ambiguous genitalia), and one with Müllerian aplasia.

Department

Pediatrics

Share

COinS