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Case Reports
. 2020 Nov;112(19):1733-1737.
doi: 10.1002/bdr2.1801. Epub 2020 Sep 15.

Prenatal diagnosis of Proteus syndrome: Diagnosis of an AKT1 mutation from amniocytes

Katherine Abell  1   2 , Leandra Tolusso  1   2 , Nicki Smith  3 , Robert Hopkin  1   2 , Marissa Vawter-Lee  1   4 , Mounira Habli  3   5 , Stefanie Riddle  1   6 , Maria A Calvo-Garcia  1   7 , Qiaoning Guan  2 , Karin Bierbrauer  1   8 , Vivian Hwa  1   9 , Howard M Saal  1   2
Affiliations
Case Reports

Prenatal diagnosis of Proteus syndrome: Diagnosis of an AKT1 mutation from amniocytes

Katherine Abell et al. Birth Defects Res. 2020 Nov.

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.

Keywords: Proteus syndrome; exome sequencing; mosaicism; prenatal diagnosis.

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