Syndromes Flashcards
VACTERL
Vertebral abnormalities
Anal atresia
Cardiac defects –
Tracheo-oEsophageal fistula
Renal defects
Limb abnormalities – hypoplasia, absent defects
Li Fraumeni syndrome
Autosomal dominant TP53 mutation on chromosome 17 (same chromosome as NF-1)
•P53 delays cell cycle progression if DNA damage detected – tumour suppressor gene
Associated tumours – “SBLA”
- Sarcoma
- Breast
- Leukaemia
- Adrenal gland -
Fanconia Anaemia
FA pathway involved in DNA repair
AR mutation in one of 13 genes (FANCA to FANCQ)
Features:
- Congenital malformations – VACTERL
- Pancytopaenia/bone marrow failure
- MDS/Leukaemia
- SCC – head, neck, oesophagus, anal, urogenital
BRCA2
Autosomal dominant
Chromosome 13
Gene to repair DNA damage
Associated tumours
Breast 69%
Ovarian 17%
Melanoma
Prostate
Gynae (uterine, fallopian tube, endometrial)
Primary peritoneal
VHL
Autosomal dominant
vHL = Tumour suppressor gene on chromosome 3 – codes for VEGF
Tumours “BRAP!”:
Brain – haemangioblastomas
Renal – clear cell, AMLs
Adrenal– phaeo, paraganglioma
Pancreas – NETs, serous cystadenoma
Generally all vascular tumours
Carney triad
Sporadic – hypermethylation of SDHC promotor
Features
- GISTs
- Paragangliomas
- Pulmonary chondromas
Phaeochromocytoma - Paraganglioma syndrome
•SDH mutation (bit like Carney dyad/triad)
Tumours:
- Phaeos
- Paragangliomas
- Non-medullary thyroid ca (cf MEN2)
- Renal cell cancer
Lynch
Germline mutation in mismatch repair genes – MLH-1, MSH-2, MSH-6, PMS-1
Associated tumours:
- Colon – right-sided, mucinous/poorly differentiated
- Ovary
- Endometrial
- Urinary tract
- Small bowel
Gorlin syndrome
Autosomal dominant
•Mutation in PTCH1 gene on chromosome 9
Features
- Multiple BCCs
- Jaw odontogenic cysts
- Cleft lip/palate
- Medulloblastomas
BRCA1
Chromosome 17
Autosomal dominant
Helps repair damaged DNA
Associated tumours
Breast >70%
Ovarian >40%
Small increased risk in pancreas and prostate
Neurofibromatosis Type 2
- NF-2 gene on Chromosome 22
- Produces merlin – tumour suppressor
- Features
- Central nerve tumours
- Meningiomas
- Vestibular schwannomas
Carney Dyad
Germline mutation in SDH (cf Carney triad)
- Autosomal dominant
- Associated tumours
- GIST
- Paragangliomas
- Lack mutations in PDGFRa or KIT
Familial Diffuse Gastric Cancer
- CDH1 mutation (codes for E-cadherin – like lobular breast ca)
- Autosomal dominant
- Associated tumours
- Diffuse gastric cancer
- Lobular breast ca
•
•Recommend prophylactic gastrectomy in 20s-30s if gene mutation identified
Carney Complex
A rare Multiple endocrine neoplasia syndrome
•Mutation in PRKAR1A gene
cf Dyad, Triad
Characterised by (LAMB)
- Lentinginous (pigmented) skin lesions
- Atrial myxoma
- Blue naevi
- Adrenocortical disease
- Sertoli cell tumours
MEN2A
aka Sipple syndrome
Autosomal dominant RET mutation on chromosome 10
Features:
- Medullary thyroid cancer - all
- Adrenal tumours, usually phaeos - 50%
- Parathyroid hyperplasia - 20%
Phenotypes
- Classic MEN2a
- MEN2a + cutaneous lichen amyloidosis
- MEN2a + Hirschsprung’s disease
- Familial medullary thyroid ca
Dysplastic Naevus syndrome (Familial mole and melanoma syndrome)
Autosomal dominant mutation in CDKN2A
Diagnostic criteria:
- Relative with malignant melanoma
- >50 naevi, some of which are atypical
- Dysplastic naevi on histology
Risk of melanoma and also pancreatic ca
Peutz Jegher syndrome
- Autosomal dominant
- Mutation in STK11 on chromosome 19
- Features:
- Multiple hamartomatous GI polyps
- Mucosal pigmentation
- Associated tumours
- Any GIT
- Breast
- Ovary
- Cervix
- Testicular
MEN1
Autosomal dominant mutation in MENIN gene on chromosome 11 (all 1s)
Associated tumours (“PPP”):
- Parathyroid hyperplasia >90%
- Pancreatic neuroendocrine tumours - 60-80%, often multi centric
- Most commonly gastrinomas -> Zollinger Ellison syndrome
- Pituitary adenomas - 15-40%, usually prolactinomas (also “P”!)
- Others – thymic carcinoids, adrenal adenomas, angiofibromas and collagenomas of skin
MEN 2B
Different (and specific) mutation in RET – MK2 domain
Like MEN2a but no parathyroid hyperplasia, instead, cutaneous features
Features:
- Medullary thyroid cancer (much earlier than 2a – ”B” = bad)
- Adrenal – phaeos
- Cutaneous – mucosal neuromas
- Marfinoid habitus
- Intestinal ganglioneuromas and megacolon
Familial Adenomatous Polyposis
Autosomal dominant - Chromosome 5 mutation in APC gene
Phenotypes: classic, attenuated, Gardner/extraintestinal
•Numerous colonic polyps, CRC risk = 100% by age 40
Other manifestations:
- Duodenal polyps – spigelman score – and duodenal cancers
- Gastric polyps – usually fundal
- Desmoids
- Hepatoblastoma
- Medulloblastoma
- CHRPE
- Sebaceous cysts
- Thyroid ca (papillary)
Muir-Torre syndrome
- Usually MSH-2 germline mutation
- Autosomal dominant
- Kind of variant of Lynch
Associated tumours
- Lynch-type colon cancers
- Keratoacanthomas
- Sebaceous adenomas and skin cancers
Neurofibromatosis Type 1
Mutation in NF-1 gene on chromosome 17
Autosomal dominant
Features:
- Café au lait spots
- Cutaneous neurofibromas
- Lisch nodules (on iris)
- Optic pathway gliomas
- Other gliomas
- Long bone dysplasia and pseudoarthrosis
Cancer associations
- Sarcoma, inc MPNST, rhabdomyo-,
- GIST
-Glomus tumours
Cowden syndrome
PTEN mutation on chromosome 10q
Features:
- Multiple hamartomas
- Cutaneous – trichilemommas, oral fibromas, palmar keratoses
Associated tumours
- Breast
- Endometrial
- Kidney
- Colorectal
- Thyroid
Castleman disease
Three distinct disorders based on the number of regions of enlarged lymph nodes with characteristic histopathologic features and the presence/absence of human herpesvirus 8 (HHV-8, also called Kaposi sarcoma associated herpesvirus [KSHV]) infection
- Unicentric
- Multicentric
- HHV-8 associated
The characteristic histopathologic features of lymph nodes from patients with Castleman disease (CD) are believed to either be exaggerations of the types of reactive changes that can be seen in response to normal antigenic stimuli or representative of a low-grade neoplastic process. These features include atrophic and hyperplastic germinal centers, follicular dendritic cell (FDC) prominence, the accumulation of immunoblasts and plasma cells, and increased vascularity.
Riley-Banayan-Ruvalcaba syndrome
PTEN mutation (cf Cowden syndrome)
Features
- hamartomas
- multiple subcutaneous lipomas
- macrocephaly
- penile lentigines
