Phenotypic Characterization of Seven Pediatric Patients Diagnosed With KAT6B-Related Disorders: Case Series and Review of the Literature

Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson Syndrome (SBBYSS) are clinically distinct neurodevelopmental disorders caused by monoallelic pathogenic variants in KAT6B. In some cases, GPS and SBBYSS features can overlap, determining an intermediate phenotype. In the present study, we describe seven patients, four with a clinical diagnosis of SBBYSS and three presenting with an intermediate phenotype. All patients carried de novo pathogenic variants in KAT6B that were identified by exome sequencing. Five variants were novel. We provide both molecular and clinical findings, highlighting the previously undescribed association with two additional features: partial penoscrotal transposition and hypopigmented macules. We performed a review of the literature, listing the clinical features of 152 patients described in 33 papers, with a molecularly confirmed diagnosis of KAT6B-related disorders, reporting the frequency of each clinical feature detected in patients diagnosed with SBBYSS and GPS. The present work provides new insights into the phenotype associated with "KAT6B-related disorders", expanding the spectrum of features that can lead to a clinical suspicion of these conditions, also guiding the molecular investigations.