Oncologic surveillance for subjects with biallelic mismatch repair gene mutations-10 year follow-up in a kindred
© Durno et al; licensee BioMed Central Ltd. 2011
Published: 10 March 2011
Lynch syndrome (LS) is caused by heterozygous germline mutations in the DNA mismatch repair (MMR) genes and is a highly penetrant autosomal dominant condition. A novel childhood cancer syndrome caused by biallelic germline MMR gene mutations and characterized by brain tumors, leukemias, gastrointestinal (GI) polyposis, GI cancer and café-au-lait spots (CALS) has been described. We reported the first biallelic kindred in which 2 of 3 siblings proven to have a homozygous germline MLH1 mutation, developed early-onset GI cancer. In contrast to LS with clear GI screening and surveillance recommendations, there are no recommendations for surveillance of individuals with biallelic mutations and no literature describing the long term outcome.
To prospectively describe long-term outcome of our two young patients with biallelic MMR mutations, and to develop a generic cancer screening protocol for other patients with biallelic MMR mutations.
On the basis of the molecular results, the 2 surviving sisters and parents of a deceased child with metastatic duodenal cancer began a surveillance protocol based on our crude estimates of cancer risks and available cancer screening modalities.
Upper GI Tract and small bowel
Video capsule endoscopy *
MRI brain q 6 months
CBC, DNA for T-cell and B-cell rearrangement, serum LDH q 3 to 6 months
Abdominal ultrasound at birth or diagnosis
Biallelic carriers who participated in oncologic surveillance had presymptomatic neoplasms identified and treated. These siblings are alive with no evidence of disease at 10-year follow-up. Aggressive surveillance in biallelic MMR carriers is feasible, allows early detection and improves long-term survival.
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