Radvanszky, J.a,b,c, Hyblova, M.b,c, Durovcikova, D.d, Hikkelova, M.eFiedler, E.fKadasi, L.a,bTurna, J.bMinarik, G.b,c, Szemes, T.b,c

aInstitute for Clinical and Translational Research, Biomedical Research Centre, Slovak Academy of Sciences, Bratislava, Slovakia
bDepartment of Molecular Biology, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia
cGeneton s.r.o, Bratislava, Slovakia
dDepartment of Medical Genetics, Slovak Medical University, Bratislava, Slovakia
eLaboratory of Medical Genetics, Alphamedical s.r.o, Bratislava, Slovakia
fInstitut für Klinische Genetik, Leitung Microarray-Diagnostik, Klinikum Stuttgart/Olgahospital, Stuttgart, Germany

Abstract

Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification.