S Ho, IFM Lo, HM Luk

Abstract

The advancement of genomic testing allows the detection of individuals affected by multilocus inherited neoplasia alleles syndrome (MINAS), a term that refers to those who harbour two or more dominant cancer predisposing germline variants. Although the phenotypic implication for MINAS is yet to be established, it is postulated that it might lead to a more severe or atypical phenotype. Herein we report 2 individuals each harbouring 2 pathogenic germline cancer predisposition gene variants. The first patient is a 18-year-old Chinese boy with likely pathogenic variants in NM_003000.2(SDHB):c.137G>A(p.Arg46Gln) and NM_000264.3(PTCH1):c.2380C>T(p.Gln794*). He has a relatively earlier onset of paraganglioma compared to the mean age of diagnosis in individuals harbouring a pathogenic SDHB mutation. The second patient is a 12-year-old Chinese boy with pathogenic variants identified in NM_000729.3(BRCA1):c.4372C>T(p.Gln1458*) and NM_000314.4(PTEN):c.1003C>T(p.Arg335*). He has clinical features of PTEN hamartoma tumour syndrome including developmental delay and macrocephaly, but enjoys good health and has no oncological disease to date.