Tumour spectrum in AKT1-related Proteus syndrome: a systematic review of clinical reports and series.

Abstract

AKT1-related Proteus syndrome is an ultra-rare mosaic overgrowth disorder with tumour predisposition. We conducted a systematic review to determine the range and characteristics of these tumours. A systematic review was conducted to identify clinical reports and clinical series of Proteus syndrome published between 1983 and 2023. Affected individuals were selected based on existing Proteus syndrome diagnostic criteria and expert review. Six databases were searched, and each unique record was screened independently by two authors. Two authors extracted the following data from each included report per individual: demographics, tumour diagnosis, characteristics, outcome, clinical features of Proteus syndrome and report of AKT1 genetic testing. The literature searches yielded 3074 records of which 1239 were unique and screened. After screening, 190 records were included. These represented 205 unique individuals with Proteus syndrome. There were 38 individuals (19%) with at least one tumour diagnosis. The average age of tumour diagnosis was 15.1 years (SD 12.1). The most frequent tumour sites were genitourinary/gynaecologic (25 tumours, 53%) followed by the central nervous system (11 tumours, 23%). Most tumours were benign and treated with surgery alone. This systematic review provides a summary of Proteus syndrome-associated tumours from the literature. These data assist clinicians in the diagnosis and prognosis of these tumours. The study highlights the knowledge gap of possible adult-onset tumours and long-term outcomes, which requires further research.PROSPERO registration number CRD42021237914.