Genetic Syndromes Flashcards
FAP
Mutation of APC gene (adenomatous polyposis coli)
Autosomal dominant - chromosome 5q
100% risk of bowel cancer
Hudreds of adenomatous poylps (defintion >100, attenuated if 10-100)
Colonic microadenomas (not seen in HNPCC)
Duodenal adenomas
Desmoid tumours
Surveillacne: flexi-sig from age 13 annually, 5-yearly colonoscopy from 20, prophylatic surgery when finished school or if symptomatic
Gardner
Gardner
HNPCC / Lynch syndrome
Lynch syndrome: Germline mutation of MMR genes (usually MLH1, MSH2,MSH6,PMS2) or EPCAM gene
HNPCC if meets Amsterdam criteria
Autosomal dominant
2-3% of all colorectal cancer
and 3% of endometrial cancer
Commonest inherited bowel cancer syndrome
in CRC, 7% have sychronous tumours, and 2%/yr rate of metanchronous tumours
CRC features: younger, more right sided, synchronous lesions, poor differentiated, signet ring and medullary subtype,
Amsterdam II criteria for HNPCC
3 relatives with Lynch syndrome associated cancers (colorectal, endometrial, small bowel, TCC of ureter and renal pelvis)
2 successive generations affected
1 colorectal cancer under 50 years
FAP excluded
Tumours verified by pathological examination
Sensitivity 22% Specificity 98%
HNPCC cancers
Large bowel 30-75%
Endometrium 30-70%
Stomach 5-10%
Ovary 5-10%
Urothelium 5%
Small bowel, pancreas, brain
MAP
MYH-associated polyposis
Autosomal recessive
Biallelic mutation of mutY human homologue gen (MYH)
Chromosome 1p
1:200 general population hetrozygus (minimal increased risk)
Multiple colonic poylps, however only 50% have >100
1–% risk of CRC by age 60
Average age of CRC 47 years
Duodenal polyps 20-30%
Increased risk of oesteoma, dental cys and breast cancer
No desmoids
Start surveillance 25, otherwise manage as per FAP
Fam juvenile polyposis syndrome
Autosomal dominant
Multiple harmatomatous polyps colon and upper GI
Macrocephaly
Hereditary haemorrhagic telangiectasia
Congentigal heart disease
SMAD4 and BMPR1A genes
40% risk of CRC
Surveillance: Regular screening with upper and lower endoscopy
Prophylactic gastrectomy and collectomy occasionally performed
MEN 1
aka Wermer’s syndrome
Autosomal dominant
MEN1 gene codes for tumour suppressor protein menin (chromosome 11)
3 Ps - primiary hyperParathyroidism, anterior Pituitary adenomas, enteroPancreatic endocrine cells but also adrenal cortical adenoma
Hyper parathyroidism - 100%by age 50, on average 20 years younger than sporadic, far more multiple tumours
MEN 2a
X
MEN 2b
x
BRCA 1
BRCA 1
BRCA 2
BRCA 2
Von Hippel-Lindau
Von Hippel-Lindau
Carney
Carney
Neurofibromatosis
Neurofibromatosis
Cowden disease
Mutation of the PTEN genen on chromosome 10q22
Gastro-intestinal harmatomas
Breast cancer
Thyroid cacner
Uterine and cervical cancer
Fibrocystic breast disease
Non-toxic goitre
Trichilemmomas and other mucocutaneous lesions
Li fraumeni
Autosomal dominant
TP53 aka tumour protein p53 (chromosome 17p13)
aka SBLA syndrome: Sarcoma, Breast, Leukaemia, Adrenal
80% lifetime risk of malignancy, 40% more than one tumour
Typically under 45 years
soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumor, adrenocortical carcinoma, leukemia, or lung bronchoalveolar cancer
Test all with choroid plexus carcinoma or adrenocorticocarcinoma and women 30 years or younger with breast cancer if BRCA -ve
Peutz Jegher
Autosomal dominant - STK11 gene on chromosome 19p13
Mucocutaneous pigmentation with multiple gastrointestinal harmatomaous polyps
Common to have small bowel obstruction from polyp intussusception
Lifetime cancer risk:
●Colorectal – 39 percent
●Stomach – 29 percent
●Small bowel – 13 percent
●Pancreas – 11 to 36 percent
●Ovary 20%, Cervix 10%, Breast 30-50%,
●Sertoli cell testicular cancer 10%
Surveillance: Annual physical and Hb check, Upper/Lower and capsule endoscopy every 2-3 years
Annual breast surveillance from 25yrs (<50 MRI/US, >50 mammogram)
