Syndromes

Question 1

list the gene, protein, pattern of inheritance and 5 lesions associated with:
Neurofibromatosis type 1

Answer 1

NF1, neurofibromin, Autosomal Dominant

Neurofibromas, plexiform neurofibromas
MPNST
Lisch nodules
Pilocytic astrocytoma
Cafe au lait spots

Question 2

List lesions associated with neurofibromatosis, type 2

Answer 2

Autosomal dominant, NF2 –> merlin

Bilateral acoustic schwannomas
Meningiomas
Spinal cord ependymomas
Cafe au lait spots (but NO lisch nodules)

Question 3

List the gene/protein, pattern of inheritance, and 5 lesions associated with tuberous sclerosis.

Answer 3

TSC1 tuberin
TSC2 hamartin
Autosomal dominant

PEComas: renal angiomyolipoma, clear cell sugar tumor of the lung, pulmonary lymphangioleiomyomatosis;

CNS: Cortical tubers, SEGA, white matter heterotopias

Cardiac rhabdomyoma

Angiofibroma
Periungual fibroma
Connective tissue nevi: peau chagrin/shagreen patch
Ash leaf patches (hypopigmented patches)

Eosinophilic, solid and cystic RCC

Question 4

List the gene, inheritance, and clinical features of Sturge Weber

Answer 4

not familial, unknown cause.

PHEOCHROMOCYTOMA
Port-wine / nevus flammeus (dilated vessels in distribution of trigeminal)

Angiomatosis of ipsilateral leptomeninges

Question 5

List the gene, pattern of inheritance, chromosome and lesions associated with:

Von Hippel Lindau

Answer 5

Autosomal dominant mutation in VHL, chromosome 3

Clear cell RCC; cysts of kidney, pancreas, liver

Hemangioblastoma

PHEOCHROMOCYTOMAS (clear cell change, CAIX and tyrosine hydroxylase)

Pancreatic neuroendocrine tumor/islet cell tumor (clear cell variant, CAIX+)

Papillary cystadenoma of epididmymis and broad ligament

Endolymphatic sac tumor of the ear

Question 6

List the gene, pattern of inheritance, and lesions associated with Birt-Hogg-Dube

Answer 6

AD
BHD gene ; chromosome 17
Folliculin protein

Renal cell tumors of VARIOUS types: clear cell, chromophobe, papillary; oncocytomas; hybrid oncocytic tumors.

Facial fibrofolliculomas and skin tags

Question 7

List the pattern of inheritance and lesions associated with Beckwith-Wiedemann syndrome.

Answer 7

(Sporadic or AD 15%) ; duplication of paternal allele (uniparental disomy) on chromosome 11

Overgrowth syndrome : organomegaly, macroglossia

Increased childhood cancers: 
Wilms tumor
Hepatoblastoma
pancreatoblastoma
neuroblastoma

Question 8

What is WAGR?

Answer 8

not familial; deletion of WT1 gene 
W: Wilms
A: Aniridia
G: genito-urinary abnormalities
R: cognitive impairment

Question 9

What is Denys-Drash? List associated lesions.

Answer 9

Not familial; WT1 point mutation

Gonadoblastoma

Wilms Tumor

Kidney: Diffuse mesangial sclerosis

Question 10

What is the mutation in familial hereditary papillary renal cell cancer?

Answer 10

Autosomal dominant inheritance of mutation in MET on 7q34

Multiple bilateral type 1 papillary RCCs

Question 11

What are features (gene, mutation, lesions) of hereditary leiomyomatosis and renal cell carcinoma syndrome?

Answer 11

FH gene: encodes fumarate hydratase

Autosomal dominant, chromosome 1

type 2 papillary RCC/FH-deficienct RCC: macronucleoli with clear halo

Leiomyomas of the uterus

Cutaneous leiomyomas

Question 12

LIst SDH-deficient tumors

Answer 12

SDH-deficient RCC

Carney-stratakis: GIST, pheochomocytoma, paragangliom, pituitary adenoma

Question 13

List lesions associated with Mazabraud

Answer 13

Fibrous dysplasia

Soft tissue/intramuscular myxoma

Question 14

List lesions seen in Maffucci syndrome

Answer 14

PTH1R mutation, not familial; (NB: Ollider related - same gene, leads to multiple enchondromas with risk of chondrosarcoma)

Multiple enchondromas
soft tissue hemangiomas

increased risk of chondrosarcoma and angiosarcoma

Question 15

What is the pattern of inheritance, gene and mechanism of FAP?

Answer 15

APC gene, autosomal dominant

normal APC gene degrades B-catenin; mutation/inactivation of APC results in B-catenin accumulation in the nucleus –> activated transcription.

Question 16

List non-colon polyp lesions seen in FAP

Answer 16

(GARDNER):
Soft tissue: fibromatosis (Desmoid tumor);
osteomas
nuchal fibroma
Gardner fibroma
Supernumerary teeth

Turcot: Medulloblastomas

Thyroid: cribriform-morular variant of PTC (young women)

juvenile nasal angiofibromas

Question 17

List three diseases associated with thymic dysplasia and/or aplasia.

Answer 17

Di George

Ataxia-telangiectasia

Severe combined immunodeficiency (SCID)

Question 18

List two paraneoplastic syndromes associated with Thymoma

Answer 18

Myasthenia Gravis

Pure red cell aplasia / erythroid hypoplasia

Question 19

List two syndromes associated with endometrioid endometrial carcinoma.

Answer 19

PTEN Cowden

Lynch