HGOS is associated with several rare and autosomal cancer predisposition syndromes, including the Li–Fraumeni syndrome (mutations of the TP53 gene), hereditary retinoblastoma (mutations of the RB1 gene), Bloom syndrome (mutations of the RECQL3 gene), Werner syndrome (mutations of the RECQL2 (WRN) gene), Rothmund–Thomson, Baller–Gerold and RAPADILINO syndromes (mutations of the RECQL4 gene). Here, WRN is linked to hereditary retinoblastoma.