Clinician’s guide to genes associated with Rett‐like phenotypes—Investigation of a Danish cohort and review of the literature

Abstract

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.