The utility of the term 'Rett-like' in relation to Rett syndrome: A systematic review.

AIM: To determine clinical features and evaluate the clinical utility of the term 'Rett-like', which is commonly used to describe individuals who do not meet the clinical criteria for a Rett syndrome (RTT) diagnosis, but exhibit some features in keeping with the diagnosis.

METHOD: A systematic review was conducted. Literature searches of Medline, CINAHL, and Embase (January 2010-December 2025) were performed, identifying individuals described as Rett-like, examining the extent to which they met major and minor RTT criteria, clinical features defined, and the linked genetic landscape.

RESULTS

In total, 166 individuals were described as Rett-like; these were predominantly female, most with no period of typical development, and a minority experienced regression. Gait abnormalities and hand stereotypies were common; loss of hand skills and speech were not. Minor RTT criteria were uncommon. A wide genetic landscape emerged, encompassing 47 different genes.

INTERPRETATION: The term 'Rett-like' commonly describes female individuals with developmental disability, typically with no period of regression, with stereotypies, abnormal gait, and seizures. The genetic landscape encompassing this disorder is broad. Clinical utility of this term is limited, with little to no evidence of diagnostic or prognostic use of 'Rett-like'.