Prenatal diagnosis of Proteus syndrome: Diagnosis of an AKT1 mutation from amniocytes. Issue 19 (15th September 2020)

• Record Type: Journal Article
• Authors: Abell, Katherine; Tolusso, Leandra; Smith, Nicki; Hopkin, Robert; Vawter‐Lee, Marissa; Habli, Mounira; Riddle, Stefanie; Calvo‐Garcia, Maria A.; Guan, Qiaoning; Bierbrauer, Karin; Hwa, Vivian; Saal, Howard M.
• Other Names: Watanabe Michiko guestEditor.; Zhou Chengji J. guestEditor.
• Is Part Of: Birth defects research. Volume 112:Issue 19(2020)
• Page Start: 1733
• Page End: 1737
• Publication Date: 2020-09-15
• Subjects: exome sequencing -- mosaicism -- prenatal diagnosis -- Proteus syndrome; Teratology -- Periodicals; Abnormalities, Human -- Periodicals; Congenital Abnormalities; Embryo, Mammalian -- abnormalities; Teratology; Abnormalities, Human; Teratology; Periodicals; Periodicals; 616.043
• DOI: 10.1002/bdr2.1801
• Languages: English
• ISSNs: 2472-1727

Abstract

Abstract: Proteus syndrome is a mosaic genetic overgrowth disorder caused by a postzygotic, mosaic activating mutation in AKT1 . Rare prenatal presentations include segmental tissue overgrowth, and skeletal and CNS anomalies. We present the first report of prenatally diagnosed and molecularly confirmed Proteus syndrome. Prenatal imaging identified megalencephaly, brain and eye malformations, focal soft tissue enlargement, and ambiguous genitalia. Exome sequencing performed on cultured amniocytes demonstrated an AKT1 pathogenic variant consistent with Proteus syndrome, and postnatal examination confirmed the diagnosis. Postnatal Sanger sequencing could not identify the AKT1 pathogenic variant. This case underscores the importance of prenatal exome sequencing on cultured amniocytes for mosaic overgrowth disorders, as well as provides additional information on the prenatal phenotype of Proteus syndrome, and highlights the impact of prenatal diagnosis on postnatal management.