Genomic Medicine

Genomic medicine is a growing area in the AKT curriculum. Questions focus on inheritance patterns, common genetic conditions, when to refer for genetic testing, and the basics of pharmacogenomics.

Inheritance patterns are commonly tested. Autosomal dominant conditions (50% chance of inheritance, affected parent): Huntington's disease, familial hypercholesterolaemia, Marfan syndrome, neurofibromatosis, polycystic kidney disease (adult type). Autosomal recessive conditions (25% chance if both parents are carriers): cystic fibrosis, sickle cell disease, thalassaemia, phenylketonuria, haemochromatosis. X-linked recessive conditions (50% of sons affected if mother is carrier): haemophilia A and B, Duchenne muscular dystrophy, G6PD deficiency, red-green colour blindness.

Genetic testing referral in primary care is indicated for patients with a strong family history of cancer (multiple first-degree relatives, young age of onset), suspected familial hypercholesterolaemia (total cholesterol above 7.5 in adults or 6.7 in children with family history), suspected inherited cardiac conditions (sudden cardiac death in a young relative), and carrier testing for conditions like sickle cell and thalassaemia.

Cancer genetics: BRCA1 and BRCA2 mutations significantly increase the risk of breast and ovarian cancer. Refer using NICE guideline CG164 criteria: 10% or greater probability of BRCA mutation based on family history. Lynch syndrome (hereditary non-polyposis colorectal cancer) increases the risk of colorectal, endometrial, and other cancers. Familial adenomatous polyposis (FAP) involves hundreds of colonic polyps and near-certain colorectal cancer without prophylactic surgery.

Pharmacogenomics affects prescribing decisions. DPYD deficiency affects metabolism of fluoropyrimidine chemotherapy (5-FU, capecitabine), leading to life-threatening toxicity. TPMT deficiency affects azathioprine metabolism and should be tested before starting treatment. CYP2D6 status affects codeine metabolism: poor metabolisers get no pain relief while ultra-rapid metabolisers are at risk of toxicity.

Prenatal screening includes the combined test (nuchal translucency, beta-hCG, PAPP-A at 11-13 weeks) for Down's, Edwards', and Patau's syndromes. Non-invasive prenatal testing (NIPT) uses cell-free fetal DNA in maternal blood and is now offered as a contingent screening test in the NHS.