Cancer Predisposition Syndromes, ASPHO Flashcards
if luekemia (or past transplant) patient, eval for CPS how?
cultured skin fibroblasts
what is variable expressivity?
range of a cancers a pathogenic varaint can produce
waht is anticipation?
age of cancer onset decreases in subsequent generations
gene for hereditary retinoblastoma?
RB1 gene
what is trilateral Rb?
rb in both eyes + embryonal midline CNS tumour= pineoblastoma
screening for hereditary rb?
eye exams under anesthesia starting at birth, until age 5
neurofibromatosis type 1 gene?
NF1
tumours with NF1?
optic pathway glioma, malignant peripheral nerve sheath tumour= MPNST, leukemia, gastroinetinal stroma tumours= GIST, bresat cancer
non-malig features of NF1? 5
iris hamartomas= lisch nodules, CAL macules, plexiform neurofibromas, axillary or inguinal freckling, macrocepahly, sphenoid wing dysplasia
gene in neurofibromatosis 2?
NF2
tumours in NF2? (3)
- bilateral vestibular schwannomas (2nd decade of life)
- meningiomas
- ependymomas
- astrocytomas
other phys exam findings on NF2?
intraderma schwannomas, retinal hamartomas, meningioma, cortical wedge cataract
nevoid basal cell carcinoma syndrome= gorlin syndrome…gene?
PTCH1 and SUFU genes
tumours seen in gorlin syndrome? 2
- desmoplastic nodular medulloblastoma (SUFU)
- basal cell carcinoma of skin
- keratogenic cysts of the jaw
- cardiac or ovarain fibromas
would you test for RB1, NF1, NF2, gorlin in kids?
yes
phys exam findings in gorlin? 3
macroceph frontal bossing facial milia coarse shaped facial features bifid ribs
von hippel-lindau syndrome: gene?
VHL
VHL tumours? 2
hemangioblastoma, retinal angioma, renal cell carcinoma, pheochromocytoma, endodermal sinus tumour (ear)
test VHL in kids?
yes
most concerning in VHL?
RCC, #1 cause of death
rhabdoid tumour predisposition type 1: gene?
SMARCB1 gene
tumours with rhabdoid tumor predispo?
Atypical teratoid/rhabdoid tumor (AT/RT), schwannomas, meningiomas, malignant rhaboid tumour of the kidney
screening in SMARCB1 muts?
brain MRI q3 months until age 5
constitutional mismatch repair def: gene?
MSH2, MLH1, MSH6, PMS2
CMMRD inheritance?
recessive! both parents have lynch syndrome!
tumours with CMMRD?
HYPERMUTATED high grade glioma, colon cancer, leuekmia
non-malig feature in CMMRD?
Cafe au lait macules
CMMRD screening?
whole body MRI yearly, cbc yearly, AUS 3 per year
Li-Fraumeni syndrome: gene? chromosome?
TP53; chrom 17
5 tumours associated with LFS?
osteosarcoma adrenocortical carcinoma ANAPLASTIC embryonal RMS choroid plexus ca breast cancer (triple pos) HYPODIPLOID pre-B ALL
screening for LFS?
- annual whole body MRI
- annual brain MRI with adn without contrast
- AUS every 3 months
- annual skin exam
Rothmund-Thomson Syndrome Type II gene?
RECQL4
Rothmund-Thomson syndroem inheritance?
AR
tumour associated with Rothmund-Thomson? ohter features?
- osteosarcoma (mulicentric)
- poikiloderma facial rash
- radial ray defects
- skeletal anomalies like frontal bossing
PTEN-Hamartoma syndrome gene? AKA?
PTEN, Cowden syndrome
PTEN-harmatoma sydnrome tumours? 2
papillary thyroid cancer
GI hamartomas
lipomas
breast cancer
ohter features in cowden sydnroem?
macrocephaly, intellectual disability, Trichilemmoma= SC lumps
multiple endocrine neoplasia type 1= MEN1..gene?
MEN1
most common tumours in MEN1?
3Ps: pancreatic neuroendocrine tumors, pituitary adenomas, parathyroid tumours
common non-malig thing seen in MEN1?
primary hyperparathyroidism
key features about tumours in MEN1?
often secrete hormones like insulin, prolactin…patient could present with low blood sugar for example
MEN2 and 2B: gene?
RET gene (activating)
tumour with BOTH MEN2A and 2B?
Pheochromocytoma, medullary thryoid cancer!…remove thyroid early! before age 5 in A, before age 1 in B!
other finding in MEN2a?
primary hyperparathyrodism
MEN4: gene?
CDKN1B gene
MEN4 tumours?
pituitary adenoma, parathyroid tumours, GU tumours
MEN4 other finding
hyperparathyroidism
DICER 1 syndrome gene?
DICER1
test for DICER in infancy?
yes
tumours in DICER1?
pleuropulmonary blastoma
cystic nephroma
sertoli-leydig cell tumour of the ovary
papillary or follicular thyroid cancer
Familial Adenomatous Polyposis (FAP): gene?
APC
cancers associated with FAP?
- hepatoblastoma
- garnder syndrome: abdo desmoid tumours
- CNS embryonal tumour= turcot syndrome
- colon cancer
screening guideline for FAP?
AUS 4x per year from birth- age 4; colonscopy starting at age 12
hereditary pheochromocytoma/paraganglioma syndrome genes?
SDHA, SDHB, SDHC, SDHD
tumours associated with hereditary pheochromocytoma/paraganglioma syndrome?
pheo RCC papillary thryroid tumours pit adenoma GIST
hereditary neurbolastoma: genes?
PHOX2B, ALK (activating), Rasopathies
PHOX2B also causes what 2 things?
central hypventilation sydnrome, hirschsprung’s disease
Genes involved inheritary wilms? (2)
WT1 and 11p15.5 lcous
5 CPS associatedi with WT and genes?
WAGR, WTI + PAX6 Denys-Drash WT1 Frasier, WT1 Perlman DIS3L2 Bohring-Opitiz Syndrome ASXL1
WAGR stands for?
wilms tumor, aniridia, GU anomalies (eg hypospadias), intelleculal disability
non WT finding in denys-dash?
kidney diffuse meangial sclerosis
2 findings in perlman other than WT?
polydactyly, fetal ascites
Bohring Opitz syndrome finding other than WT
intellectual disability
if pt has a WT predispo, screening to do?
renal ultrasounds every 3 months from birth to age 7
WT1 looked on which chrom?
11
Bloom syndrome: gene?
BLM
Bloom syndrome inheritance?
AR
tumours in Bloom?
WT, GI/colon, bresat cancer, leukemias
concner when treating bloom sydnrome pt for cancer?
increased tox to rad adn chemo
phys exam findings in bloom?
- narrow face
- butterfly rash at nose
- telangiectaias
- CALs
- photosensitvity
Beckwith-Wiedemann Syndrome: due to?
imprinting defect on 11p15.5
confirm BWS how?
DNA mehtylation profile
solid tumours in BWS?
HBL, WT
screening for BWS?
-AUS adn AFP a 3 months from birth to age 4…after age 4, just do RENAL US q 3 months –>through age 7
BWS screening has same screening as what two other syndromes?
Simpson-Golabi-Behmel syndrome & T18
phys exam features in BWS?
large tongue hemihypertrophy omphalocele splenomegaly/visceromegaly macrocephaly
FH tumour predisoposition syndrome: gene?
fumarate hydratase (FH)
another name for FH tumour predisp syndrome?
hereditary leiomyomatosis and renal cell carcinoma
RHabdoid tumour predispositon syndrome TYPE TWO caused by what gene mut?
SMARCA4
tumour associated with RHabdoid tumour predispositon syndrome TYPE TWO?
small cell ca of the ovary- hypercalcemic type
noonan syndrome: gene causes?
PTPN11 gene, SOS1, RAF1, KRAS
leuks associated iwth nnonan?
JMML> ALL
noonan features on phys exam?
S’s:
Short stature/strabismus/short neck/shield chest/Setting of ears is low
short stature strabismus shield chest short neck high palate low set ears
familila plt disorder with associated myeloid malig: gene?
RUNX1
mutation associated iwth familila plt disorder with associated myeloid malig?
MDS/AML, can see monosomy 7
familial plt disorder with associated myeloid malig: exhbits what CPS feature?
anticipation
familial plt disorder with associated myeloid malig: see waht with plts?
asprin-like plt defect, mild thrombocytopenia, can mimic ITP
THrombocytopenia 5: gene?
ETV6
Thrombocyteopnia 5 associated with what cancers?
pre-B ALL (HYPERdiploid ALL), MDS/AML
features of thrombocytopenia 5?
mild thrombocytopenia, mild bleeding phenotype
ANKRD26-related thrombocytopenia gene?
ANKRD26
ANKRD26: aka?associated iwth what cancer? phenotype?
Thrombocytoepnia 2; AML; mild thrombocytopenia, mild bleeding phenotype
CEBPA-asscoiated familila AML: associated with? CPS feature?
AML; highly penetraint, should have fam hx of AML…should see 2 CEBPA variants on leukemia sequencing and 1 variant on germline sequencing
