Autosomal dominant transmission.

Synopsis

 Predispsotion to tumors (unusually early age of tumor onset frequent multiple primary tumors)

• soft tissue sarcomas
• breast carcinomas
• brain tumors
• osteosarcoma
• embryonal rhabdomyosarcoma
• leukemias
• adrenocortical carcinoma
• lymphomas
• pulmonary adenocarcinoma
• melanoma
• gonadal germ cell tumors
• prostate carcinomas
• pancreatic carcinomas

 Impaired lymphocyte transformation with phytohemagglutinin
 Polyclonal IgM elevation

Etiology (3 known loci)

 Locus 9p21
 Locus TP53 at 17p13.1: germline mutations in the TP53 gene coding for protein p53
 Locus CHEK2 at 22q12.1: germline mutations in the CHEK2 gene (MIM.604373). CHEK2 is a protein kinase activated in response to DNA damage, is involved in cell cycle arrest.