SYNDROMES OF TUMOR SUPPRESSION

Question 1

Basal Cell Nevus Syndrome (Gorlin Syndrome)

Answer 1

AD, P TCH (PATCHED) gene, inhibits sonic hedgehog signaling (unbound PTCH inhibits Smoothened (SMO) signaling;
-bifid ribs, calcification of falx cerebrum, agenesis of corpus callosum, ovarian fibromas, medulloblastoma, meningioma

Question 2

Neurofibromatosis, Type I (Von Recklinghausen Disease)

Answer 2

AD, NF-1 gene, encodes neurofibromin

Question 3

Neurofibromatosis, Type II

Answer 3

AD, NF-2 gene, encodes merlin/schwannomin
• Diagnosis requires bilateral CNVII masses OR first degree relative AND either unilateral CN VIII mass OR two of the following: schwannoma, optic glioma, meningioma, juvenile posterior subcapsular opacity

Question 4

Carney Syndrome (NAME or LAMB Syndrome)

Answer 4

AD, PRKAR1A gene, psammomatous melanotic schwannomas
NAME : nevi, atrial myxoma, myxoid tumors, ephelides
LAMB : lentigines, atrial myxomas, mucocutaneous myxomas, blue nevi

Question 5

Muir–Torre Syndrome

Answer 5

AD, mutation in M LH1 and MSH2 (DNA mismatch repair genes)
• Multiple sebaceous neoplasms and keratoacanthomas
• ↑ Risk of colon adenocarcinoma

Question 6

Tuberous Sclerosis

Answer 6

AD, TSC1 gene mutation (hamartin), and TSC2 (tuberin)
Ash-leaf macules (earliest finding), facial angiofibromas, connective tissue nevi (shagreen patch), fibromas (gingival and subungual), CALMs, dental enamel pits, pulmonary
lymphangioleiomyomatosis , cortical tubers, cardiac rhabdomyoma

Question 7

Cowden Syndrome (Multiple Hamartoma Syndrome)

Answer 7

AD, PTEN gene mutation, encodes tyrosine phosphatase protein
• ↑ Breast fi broadenoma, ↑ CA: b reast , thyroid follicular ; GI polyps
COWden – trichileMOOmas; other PTEN syndromes: Lhermitte–Duclos and
Bannayan–Zonana syndrome

Question 8

MEN Type 1 (Wermer Syndrome

Answer 8

– AD, MEN1 mutation (menin: tumor suppressor)
– Angiofi bromas, collagenomas, lipomas, CALMs
– Pituitary, parathyroid, pancreatic tumors

Question 9

MEN Type 2a (Sipple Syndrome)

Answer 9

AD, RET mutation (tyrosine kinase receptor)
– Lichen or macular amyloidosis , hemangiomas,
genital lentigines, hamartomas, lipomas
– Parathyroid tumor, thyroid medullary carcinoma ,
pheochromocytoma

Question 10

MEN Type 2B (Multiple Mucosal Neuroma Syndrome)

Answer 10

– AD, RET mutation
– Multiple mucosal neuromas , thickened lips
– Thyroid medullary carcinoma, pheochromocytoma, marfanoid habitus, diffuse ganglioneuromatosis (megacolon, diarrhea)

Question 11

Bannayan–Riley–Ruvalcaba Syndrome

Answer 11

• AD, PTEN mutation
• Genital lentigines, hamartomas, lipomas, hemangiomas, mental retardation,
macrocephaly

Question 12

LEOPARD Syndrome (Multiple Lentigines Syndrome)

Answer 12

• AD, PTPN11 gene mutation, encodes tyrosine phosphatase Shp2
• Lentigines, ECG abnormalities, ocular hypertelorism, pulmonic stenosis,abnormal genitalia, retarded growth and deafness

Question 13

Peutz–Jeghers Syndrome

Answer 13

• AD, STK11/LKB1
• Hyperpigmented macules on lip/oral mucosa/fingers (starts in infancy/early childhood) and intestinal polyposis (± bleeding, intussusception)
• ↑ GI adenocarcinoma , ↑ other solid organ malignancies

Question 14

Gardner Syndrome

Answer 14

AD, APC
• Cutaneous epidermoid cysts, osteomas (mandible, maxilla), supernumerary teeth, odontomas, fibromas, congenital hypertrophy of the retinal pigment epithelium (CHRPE)
• Tumors: GI adenocarcinoma (inevitable), osteochondromas, thyroid papillary carcinoma, hepatoblastoma, adrenal adenomas

Question 15

Birt–Hogg–Dubé Syndrome

Answer 15

• AD, BHD gene (encodes folliculin)
• Multiple fibrofolliculomas, trichodiscomas, acrochordons on the face, scalp, neck, and upper trunk
• Associated with renal cell carcinoma, medullary carcinoma of thyroid, spontaneous pneumothorax (multiple pulmonary cysts)

Question 16

Dysplastic Nevus Syndrome

Answer 16

• AD, CDKN2A (p16 tumor suppressor gene, inhibits cyclin-dependent kinase 4 [CDK4])
• Dysplastic nevi, melanoma, pancreatic CA, astrocytomas