Clinician's guide to genes associated with Rett-like phenotypes - Investigation of a Danish cohort and review of the literature

TY - JOUR

T1 - Clinician's guide to genes associated with Rett-like phenotypes - Investigation of a Danish cohort and review of the literature

AU - Schönewolf-Greulich, Bitten

AU - Bisgaard, Anne-Marie

AU - Møller, Rikke S

AU - Dunø, Morten

AU - Brøndum-Nielsen, Karen

AU - Kaur, Simran

AU - Van Bergen, Nicole J

AU - Lunke, Sebastian

AU - Eggers, Stefanie

AU - Jespersgaard, Cathrine

AU - Christodoulou, John

AU - Tümer, Zeynep

N1 - This article is protected by copyright. All rights reserved.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - The differential diagnostics in Rett syndrome has evolved with the development of next generation sequencing-based techniques and many patients have been diagnosed with other syndromes or variants in newly described genes where the associated phenotype(s) is yet to be fully explored. The term Rett-like refers to phenotypes with distinct overlapping features of Rett syndrome where the clinical criteria are not completely fulfilled. In this study we have combined a review of Rett-like disorders with data from a Danish cohort of 35 patients with Rett-like phenotypes emphasizing the diagnostic overlap with Pitt-Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants. We also found a patient with a pathogenic variant in KCNB1, which has not been previously linked to a Rett-like phenotype. This study underlines the clinical and genetic heterogeneity of a Rett syndrome spectrum, and provides an overview of the Rett syndrome-related genes described to date, and hence serves as a guide for diagnosing patients with Rett-like phenotypes.

AB - The differential diagnostics in Rett syndrome has evolved with the development of next generation sequencing-based techniques and many patients have been diagnosed with other syndromes or variants in newly described genes where the associated phenotype(s) is yet to be fully explored. The term Rett-like refers to phenotypes with distinct overlapping features of Rett syndrome where the clinical criteria are not completely fulfilled. In this study we have combined a review of Rett-like disorders with data from a Danish cohort of 35 patients with Rett-like phenotypes emphasizing the diagnostic overlap with Pitt-Hopkins syndrome, Cornelia de Lange syndrome with SMC1A variants, and epileptic encephalopathies, for example, due to STXBP1 variants. We also found a patient with a pathogenic variant in KCNB1, which has not been previously linked to a Rett-like phenotype. This study underlines the clinical and genetic heterogeneity of a Rett syndrome spectrum, and provides an overview of the Rett syndrome-related genes described to date, and hence serves as a guide for diagnosing patients with Rett-like phenotypes.

KW - Journal Article

KW - Review

KW - MECP2

KW - Atypical Rett

KW - CDKL5

KW - RTT

KW - KCNB1

KW - Rett-like

KW - FOXG1

KW - SMC1A

U2 - 10.1111/cge.13153

DO - 10.1111/cge.13153

M3 - Review

C2 - 29023665

SN - 0009-9163

VL - 95

SP - 221

EP - 230

JO - Clinical Genetics

JF - Clinical Genetics

IS - 2

ER -