Syndromes Flashcards

1
Q

Familial retinoblastoma

A

Ch 13

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2
Q

Familial adenomatous polyposis

A

aka familial polyposis coli

5q21

can have desmoid tumors (aggressive fibromatosis)

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3
Q

MEN 1

A

11p13 (MEN1 tumor suppressor gene)

autosomal dominant

aka Werner syndrome

3 P’s (parathyroid, pancreas, pituitary)

  • primary hyperparathyroidism (hypercalcemia –> kidney stones) - hyperplasia or adenomas
  • pancreatic microadenomas, gastrinomas (Zollinger-Ellison syndrome), insulinomas
  • pituitary adenomas (esp prolactinoma)
  • other: duodenal gastrinomas (> pancreatic), carcinoid tumors, thyroid and adrenocortical adenomas, lipomas, thyroid C-cell hyperplasia
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4
Q

MEN 2

A

RET proto-oncogene (10q12)

MEN 2A (Sipple Syndrome):

  • pheochromocytoma (40-50%, bilat, extra-adrenal)
  • medullary thyroid carcinoma (100%)
  • primary hyperparathyroidism (10-20%)

MEN 2B (aka MEN-3)

  • medullary thyroid carcinoma (multifocal, more aggressive than in MEN-2A)
  • pheochromocytomas
  • neuromas or ganglioneuromas involving the skin, oral mucosa, eyes, respiratory tract, and gastrointestinal tract
  • marfanoid habitus

Familial medullary thyroid cancer

  • variant of MEN-2A w/ strong predisposition to medullary thyroid cancer (older age, more indolent) but not the other clinical manifestations of MEN-2A or MEN-2B. A substantial majority of cases of medullary thyroid cancer are sporadic, but as many as 20% may be familial.

* prophylactic thyroidectomy

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5
Q

Neurofibromatosis

A

NF 1 (von Recklinghausen neurofibomatosis)

  • neurofibromin gene (ch 17)
  • autosomal dominant
  • cafe-au-lait spots, neurofibromas, Lisch nodules, optic glioma, osseous lesions, macrocephaly, short stature and mental retardation

NF 2 (MISME Syndrome”, for “Multiple Inherited Schwannomas, Meningiomas, and Ependymomas”)

  • Merlin (schwannomin) gene 22q11
  • bilateral vestibular schwannomas, tumors of other cranial nerves/meninges, tumors of spinal cord (intramedullary - astrocytomas & ependymomas; extramedullary - schannomas & meningiomas), juvenile subcapsular cataracts
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6
Q

Von Hippel-Lindau disease

A

VHL tumor suppressor gene (3p25-26)

  • autosomal dominant
  • retinal and CNS hemangioblastomas
  • retinal angiomatosis –> retinal detachment
  • pheochromocytomas
  • multiple cysts in pancreas and kidneys
  • clear cell renal cell carcinoma
  • pancreatic neuroendocrine tumors
  • endolymphatic sac tumors
  • epididymal papillary cystadenomas
  • cafe-au-lait spots
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7
Q

Turcot’s syndrom

e

A
  • aka brain tumor-polyposis syndrome or glioma-polyposis syndrome
  • autosomal recessive (FAP with brain tumors)
  • HNPCC genes (DNA mismatch/repair defect)
  • coexistence of a hereditary colon cancer syndrome (like FAP or HNPCC) and CNS tumors
  • FAP - medulloblastoma > astrocytoma > ependymoma
  • HNPCC - GBM
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8
Q

DNA Repair Defect Syndromes

A
  • Xeroderma pigmentosa - 9, 19, 11, 16, 13
  • Ataxia-telangiectasia - 11q22.3
  • Bloom’s syndrome - 15q26.1
  • Fanconi’s anemia - 9, 16, 3, 6

* all are autosomal recessive

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9
Q

xeroderma pigmentosum

A
  • autosomal recessive d/o of defective DNA repair (nucleotide excision repair)
  • 7 repair genes (XPA-XPG)
  • inc risk of skin cancer (melanoma, SCCa, BCCa, fibrosarcoma) after UV light exposure (UV radiation –> crosslinking of pyrimidine residues, preventing normal DNA replication)
  • 9q22 and others (19, 11, 16, 13)
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10
Q

Ataxia-telangiectasia

A
  • aka Louis-Bar syndrome
  • defect in ATM(ataxia-telangiectasia mutated) gene - 11q22
  • autosomal recessive d/o of defective DNA repair
  • Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis. Several of these targets, including p53, CHK2 and H2AX are tumor suppressors.
  • neurodegenerative (progressive cerebellar ataxia)
  • mucocutaneous telangiectasias (on sclerae and skin)
  • recurrent upper resp tract (sinopuulmonary) infxn
  • inc risk CANCER (esp leukemia/lymphoma, pancreatic ductal adenoca, )
  • impaired organ maturation, increase x-ray sensitivity
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11
Q

Bloom’s syndrome

A
  • aka congenital telangiectatic erythema
  • autosomal recessive d/o of defective DNA repair
  • telangiectases and photosensitivity, growth deficiency of prenatal onset, variable degrees of immunodeficiency, and increased susceptibility to neoplasms of many sites
  • mutation in BLM gene - 15q26.1 - a DNA helicase that participates in DNA repair by homologous recombination
  • Increased sister chromatid exchanges and chromosomal instability also occur, which is assumed to be responsible for the phenotype and the cancer predisposition
  • growth delay
  • cancer risk 150-300x general pop
  • 20% develop malignancies (eg, acute myeloid leukemia, lymphoma, gastrointestinal adenocarcinoma)
  • decreased immunoglobulin A and immunoglobulin M, with recurrent respiratory and gastrointestinal tract infections
  • bird-like facies, short stature
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12
Q

Fanconi’s anemia

A
  • autosomal recessive d/o of defective DNA repair
  • 15 diff genes (FANCB is X-linked recessive, the rest are AR) - chromosomes 9, 16, 3, 6
  • most frequently reported of the rare inherited bone marrow failure syndromes
  • hemorrhages, infections, leukemia, myelodysplastic syndrome, liver tumors, and other cancers.
  • birth defects (dangling thumbs, facies, dislocated hips), kidney and heart defects
  • aplastic anemia, MDS, AML, head and neck squamous cell carcinoma (HNSCC), liver tumors (adenomas and hepatomas; primarily but not exclusively in patients who had aplastic anemia that was treated with oral androgens), vaginal squamous cell carcinoma (SCC), and brain tumors
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13
Q

Denys-Drash syndrome

A
  • gonadal dysgenesis
  • nephropathy
  • Wilms tumorz

The cause of DDS is most commonly (96% of patients) an abnormality in the WT1 gene

The presenting characteristics of DDS include loss of playfulness, decreased appetite, weight loss, growth delay, abnormal skeletal development, insomnia, abdominal pain, constipation, and anuria.

Clinically, Denys–Drash is characterized by the triad of pseudohermaphroditism, mesangial renal sclerosis, and Wilms tumor. The condition first manifests as early nephrotic syndrome and progresses to mesangial renal sclerosis and ultimately renal failure, usually within the first three years of life.

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14
Q

Li-Fraumeni syndrome

A
  • rare autosomal dominant hereditary disorder.
  • also known as the Sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome.
  • persons with Li–Fraumeni syndrome have an approximately 25-fold increased risk of developing a malignant tumor by age 50 than the population average, and are at risk for a wide range of malignancies, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft tissue sarcomas, bone sarcomas, and adrenal cortical carcinoma
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15
Q

Cushing’s syndrome

A

high ACTH, adrenal cortical adenomas

can get small cell lung cancer

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16
Q

Pt with adrenal cortical adenoma, excess aldosterone (hypernatriemia, hypokalemia, HTN)

A

Conn’s syndrome

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17
Q

Patient with tumor and hypoglycemia

A

fibrosarcoma, solitary fibrous tumor, HCC, insulinoma

overproduction of insulin or insulin-like growth factors

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18
Q

Pt has tumor and is polycythemic

A

renal cell carcinoma

cerebellar hemangioblastoma

HCC

leiomyoma

solitary fibrous tumor

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19
Q

acanthosis nigrans

A

predispostion to gastric carcinoma, lung carcinoma, uterine carcinoma

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20
Q

Pt with skin lesions and acoustic neuromas

A

NF-2!

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21
Q

Pt with rhabdomyoma or angiomyolipoma

A

Tuberous sclerosis

ch 9 & 16

cortical tubers, sclerosis, SEGAs (subependymal giant cell astrocytoma), cardiac rhabdomyomas, pulm LLM (lymphangioleiomyomatosis), AMLs, sebaceous adenomas, ash green patches, subungual fibromas

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22
Q

Pt with cavernous hemangioma and renal cell carcinoma

A

von Hippel Lindau

3p25

RCC (bilateral), papillary cystadenoma of pancreas, pheos, cavernous hemangiomas/hemangioblastomas of retaina/cerebellum/brainstem, hemangiomas/cysts of pancreas, skin, liver, kidney

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23
Q

Gardner’s syndrome

A

colonic adenomas, osteomas, desmoplastic fibromas, fibromatosis

loss of regulation

FAP & jaw osteomas

desmoids, cysts of skin, soft tissue tumors (desmoplastic fibromas)

papillary thyroid carcinoma (according to endocrine osler notes)

Inactivation of APC tumor supressor gene in Gardner or sporadic fibromatosis
leads to accumulation of nuclear beta-catenin

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24
Q

Cowden syndrome

A

aka multiple hamartoma syndrome

mutation of PTEN gene on 10q23 (same as MEN II, MEN1 11p13)

9q22.3

hamartomatous neoplasms of skin, mucosa, GI/GU tracts, CNS, bones

Trichelemmomas ,oral mucosal papillomatosis, acral and palmoplantar keratoses, increased risk of thyroid and breast cancer (> colon and renal cell carcinoma)

thyroid adenomatoid nodules and follicular neoplasms (according to osler endocrine notes)

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25
Q

Peutz-Jeghers syndrome

A

mutation in STK11 gene on chromosome 19

hamatomatous polyps (esp small bowel) and oral mucocutaneous pigmentation

women: SCTATs (sex cord tumors with annular tubules), adenoma malignum of cervix
- men: large cell calcifying sertoli cell tumors

inc risk: breast, lung, ovary, pancreas and uterine Ca; rare malignant tranmsformaion in GI tract

mnemonic “PASS Boards”: Pancreas, Adenoma malignum of cervix, Sex cord tumors, Sertoli tumors, Breast

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26
Q

Cronkite-Canada syndrome

A

non-inherited

FAP (hamartomatous polyp[s) with skin and nail changes

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27
Q

Fabry’s disease

A
  • X-linked recessive sphingolipidosis
  • deficiency of alpha-galactosidase A
  • angiokeratomas, renal insufficiency, cardiac failure
  • vacuolated myocytes
  • EM: intralysosomal dense lamellae (zebra bodies)
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28
Q

Carney’s syndrome/complex

A
  • cutaneous & cardiac myxomas (myxoid FAs)
  • spotty skin pigmentation (lentigines & blue nevi)
  • Endocrine overactivity &/or tumors (adrenal, testicular, thyroid, pituitary - acromegaly, hypercortisolemia, sexual precocity)
  • large cell calcifying Sertoli cell tumor
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29
Q

Carney’s triad

A
  • Multiple Pulmonary chondromas (hamartomas)
  • extra-adrenal_ P_aragangliomas
  • GISTs of the stomach
  • Think: Peter, Paul, and Gary
  • nonfamilial
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30
Q

Tuberous sclerosis complex

A
  • TSC1 gene (hamartin) on chromosome 9
  • TSC2 gene (tuberin) on chromosome 16
  • autosomal dominant, variable penetrance
  • non-malignant tumors (brain, kidney, heart, lung, skin), seizures, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease
  • Cardiac rhabdomyomas
  • Renal angiomyolipomas
  • Brain tumors (giant cell astrocytoma, cortical tubers, sub-ependymal nodules
  • Lung - lymphangioleiomyomatosis)
  • Skin - facial angiofibromas (adenoma sebaceum), periungual fibromas (Koenen’s tumors), hypomelanic macules (“ash leaf spots”), Shagreen patches
  • Retinal lesions - astrocytic hamartomas (“phakomas”)
  • Other eye manifestations - coloboma, eyelid angiofibromas, papilledema
31
Q

Marfan syndrome

A

defect of fibrillin-1 (in elastic fibers)

autosomal dominant connective tissue disorder

long limbs, dislocated lenses and the aortic root dilation

ectopia lentis (subluxated lens)

cystic medial degeneration of heart valves (mitral valve prolapse)

aortic dissection

spontaneous pneumothorax

32
Q

POEMS syndrome

A

Polyneuropathy

Organomegaly

Endocrinopathy

Monoclonal gammopathy

Skin changes

  • sometimes seen in pts with multicentric Castleman’s disease
33
Q

A1-antitrypsin deficiency

A
  • Autosomal recessive
  • PiSZ, PiSS, PiMZ (chromosome 14)
  • “Mmm, Mmmm Good” (2 M alleles = good prognosis)
  • “PiZZ Poor” (2 Z alleles = bad prognosisi)
  • Not too little but defective antitrypsin (a protease inhibitor that normallyl protects tissues from neutrophil elastase which breaks down elastin)
  • Cholestatic & hepatitic changes
  • pulmonary emphysema
  • periportal PAS/D+ inclusions
34
Q

Dubin-Johnson syndrome

A

autosomal recessive

Impaired biliary excretion of bilirubin glucuronides due to mutation in canalicular multidrug resistance protein 2 (MRP2)

Pigmented cytopasmic globules;?epinephrine metabolites

clinical course: innocuous; conjugated hyperbilirubinemia

** the only conjugated hyperbilirubinemia with liver pathology - BLACK LIVER

35
Q

Rotor syndrome

A

Autosomal recessive

Decreased hepatic uptake and storage?
Decreased biliary excretion?

No liver pathology

Clinical course: Innocuous; conjugated hyperbilirubinemia

36
Q

Crigler-Najjar syndrome type I

A

Autosomal recessive

Absent UGT1A1 (UGT, uridine diphosphate-glucuronyltransferase) activity

No liver pathology

Unconjugated hyperbilirubinemia

Fatal in neonatal period

37
Q

Crigler-Najjar syndrome type II

A

Autosomal dominant with variable penetrance

Decreased UGT1A1(UGT, uridine diphosphate-glucuronyltransferase) activity

No liver pathology

Clinical: Generally mild, occasional kernicterus

Unconjugated hyperbilirubinemia

38
Q

Gilbert syndrome

A

Autosomal recessive

Decreased UGT1A1 (UGT, uridine diphosphate-glucuronyltransferase) activity

No liver pathology

Unconjugated hyperbilirubinemia

Innocuous

39
Q

Hemochromatosis

A

autosomal recessive

HFE gene missense mutations (6p21; within HLA-1 region)

C282Y (cysteine –> tyrosine) = highest iron overload

H63D (histidine –> aspartate) = lowest iron overload

compound heterozygotes (C282Y and H63D) = intermediate

Northern European males

Fe accum in hepatocytes in znoe 1, then 2, and 3, and finally in bile ducts (longstanding)

Mechanism: causes inc absorption of Fe from basolateral membrane of enterocytes

Presents age 30-50 (fatigue, impotence, arthralgia, hepatomegaly, diabetes)

Complications: cirrhosis, hepatocellular carcinoma, congestive heart failure, cardiac arrhythmias, diabetes mellitus (Bronze Diabetes), Hypogonadism, Impotence, amenorrhea (pituitary), Arthropathy, Thyroid dysfunction, Sepsis

40
Q

Wilson’s disease

A

“hepatolenticular degeneration”

autosomal recessive

ATP7B gene (Wilson dz protein) on chromosome 13

Impaired ability of hepatocytes to link copper to ceruloplasma and secrete it into bloodstream

ceruloplasmin is still secreted, but in a form that lacks copper (termed apoceruloplasmin) and is rapidly degraded in the bloodstream

Inc copper in liver –> chronic active hepatitis –> cirrhosis

Unbound copper secreted into blood –> kidneys, eyes, brain (basal ganglia - lenticular nuclei - putamen, globus pallidus)

Sx: ages 6-20; encephalopathy, cirrhosis, neuropsych, Kayser-Fleischer rings, cataracts, renal tubular acidosis, cardiomyopathy, hypoparathyroidism

EM: Enlarged abnl mitochondria

Low ceruloplasmin levels

41
Q

Hereditary hemorrhagic telangiectasia (HHT)

A
  • aka Osler-Weber-Rendu syndrome
  • autosomal dominant
  • mucosal & skin telangiectasias (mouth, nose, GI, lips, nose, fingers)
  • nosebleeds
  • AVMs in large organs (lung, liver, brain)
  • KNOW: oral telangiectasias + Fe def anemia
  • %age have SMAD4 (gene: MADH4) mutation - juvenile polypsis-HHT overlap syndrome
42
Q

Henoch-Schonlein purpura

A
  • # 1 form of systemic vasculitis in kids
  • 90% of cases = kids
  • usually self-limited
  • tetrad:
    1. palpable purpura in pt with neither thrombocytopenia nor coagulopathy
    1. arthritis/arthralgia
    1. abdominal pain
    1. renal disease
  • immune mediated leukocytoclastic vasculitis assoc with IgA deposition
  • underlying cause unknown but triggers include infections, immunizations, other antigens
  • IF: IgA, C3, fibrin deposits in walls of vessels
43
Q

osteogenesis imperfecta

A
44
Q

Deficiencies of platelet dense granules

A
  1. Chediak-Higashi

Autosomal recessive
Microtubule polymerization defect  decrease in phagocytosis
Recurrent pyogenic infections (Staph most common), oculocutanous albinism, peripheral neuropathy, bleeding
Giant granules in granulocytes and melanocytes

  1. Hermansky-Pudlak
  • Autosomal recessive
  • Oculocutaneous albinism, bleeding, systemic problems (pulmonary fibrosis, colitis) secondary to lysosomal dysfunction (organs accum. ceroid lipofuscin)
  • Swiss cheese platelets
    3. Wiscott-Aldrich

X-linked recessive

small granulated platelets + Fe deficiency anemia

thrombocytopenia, infection, eczema

inc risk of malignancy

45
Q

Kasabach-Merritt syndrome

A

aka “hemangioma with thrombocytopenia”

association of vascular tumor with consumptive thrombocytopenia

46
Q

21-hydroxylase deficiency

A

causes 95% of congenital adrenal hyperplasia

deficient cortisol & aldosterone (hypotension, salt wasting), leads to increased ACTH

high 17-OH progesterone

females have ambiguous genitalia at birth

“non classical” or “late onset” = mild deficiency (hirsutism and menstrual problems) that presents at puberty; can look like PCOS

47
Q

11-beta-hydroxylase deficiency

A

2nd most common cause of CAH

low cortisol and aldosterone but high ACTH leads to accumulation of 11-deoxycorticosterone (weak mineraocorticoid effects) leading to sx of mineralocorticoid excess –> no salt wasting, pts get HTN, hypokalemia instead)

accum of DHEA –> androstenedione and testosterone (virilization - females have masculinized external genitalia)

48
Q

3-beta-hydroxysteroid dehydrogenase deficience

A

rare cause of CAH

accumulation of pregnanetriol

Sx: Addison’s disease; males with female external genitalia in complete form, impotence and infertility in partial form

49
Q

17-alpha-hydroxylase deficiency

A

rare

low cortisol, inc ACTH, accum of corticosterone (HTN, hypokalemia)

diminished adrenal androgen production and estrogen production leading to hypogonadism in females and pseudohermaphroditism in males (males with female external genitalia)

50
Q

Gorlin’s syndrome

A

Aka nevoid basal cell carcinoma syndrome, Gorlin-Goltz syndrome

Autosomal dominant

Body overgrowth, jaw keratocysts, skeletal abnormalities (palmar and plantar pits), predisp to neoplasms (multiple BCCs)

Germline mutation in PTC gene on ch9q22.3

Two major, or one major and two minor criteria are essential for diagnosis.

Major criteria:
● Multiple (>2) basal cell carcinomas or one under 20 years
● Odontogenic keratocysts of the jaws proven by histopathology
● Palmar or plantar pits (3 or more)
● Bilamellar calcification of the falx cerebri
● Bifid, fused or markedly splayed ribs
● First degree relatives with this syndrome

Minor criteria:
● Macrocephaly determined after adjustment for height
● Congenital malformation: cleft lip or palate, frontal bossing, “coarse face”, moderate of severe hypertelorism
● Other skeletal abnormalities: sprengel deformity (high scapula), marked pectus deformity, marked syndactyly of the digits
● Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defects of the hands and feet, or flame-shaped lucencies of the hands or feet
● Ovarian fibroma (or cardiac fibroma)
● Medulloblastoma

51
Q

Naxos syndrome

A

Diffuse palmoplantar keratoderma with woolly hair and arrhythmogenic right ventricular cardiomyopathy

1 person in 1000 in the Hellenic islands

It has been associated with mutations in the genes encoding desmoplakin and plakoglobin.[2]

52
Q

Peutz-Jegher syndrome

A

Autosomal dominant

STK11 (LKB1)
at 19p13

GI tract: Hamartomatous polyps

Extraintestinal lesions: Up to 40% risk of CRC
and >50 % risk of Breast
CA. Also pancreatic and
gastric CA

53
Q

Familial Juvenile Polyposis

A

Autosomal dominant

SMAD4 or BMPR1A

Hamartomatous polyps

>50% risk of GI CA
including small bowel
and stomach

54
Q

Cronkhite-Canada
syndrome

A

no known mutated gene

hamartomatous polyps

Severe disease,
electrolyte imbalance and
protein loss; often fatal,

55
Q

Cowden’s disease

A

Autosomal dominant

PTEN at 10q23

Hamartomatous
polyps

Up to 50% risk of breast
CA, up to 10% risk for
thyroid CA and unknown
risk of CRC

56
Q

Familial Adenomatous Polyposis

A

Autosomal dominant

APC gene

GI tract: CRC, fundic gland
polyps, duodenal
adenomas, and CA
100% risk of CRC.

Up to 5 % risk of
duodenal CA

57
Q

Hamartomatous GI polyposis syndromes

A

Peutz-Jegher syndrome

Familial juvenile polyposis

Cronkhite-Canada syndrome

Cowden’s disease

58
Q

Gardner syndrome

A

Autosomal dominant

APC gene

Same GI lesions as FAP +
osteomas, epidermoid
cysts. fibromas, and
desmoid tumors

59
Q

Turcot syndrome

A

66% autosomal dominant
33% autosomal recessive

APC gene

Same GI lesions as FAP + PNET of CNS &
Glioblastoma multiforme

60
Q

Hereditary nonpolyposis colorectal carcinoma (HNPCC)

A

Type I (Lynch Syndrome I)

Autosomal dominant

  • MLH1 (39%)
  • MSH2 (38%)
  • MSH6 (6%)
  • PMS2 (7%)
  • ?? (5%)

CRC at age < 50 years (traditional thought) but now
many pts known to present >50 years of age

No extraintestinal lesions

Type II (Lynch Syndrome II or familial cancer Syndrome)

same as Type I + other cancers: Endometrial, gastric, small bowel, HCC, cholangioCA, pancreas, ovary,
renal pelvis, brain, and skin

61
Q

Ollier’s disease

A

Multiple enchondromata

62
Q

Maffucci’s syndrome

A

Mutliple enchondromata + angiomata (hemangiomas, lymphangiomas of skin, soft tissue, organs, etc)

also higher incidence of other malignancies, esp soft tissue and GU tract

63
Q

McCune-Albright syndrome

A

polyostotic fibrous dysplasia

endocrinopathies (esp precocious puberty in females; also hyperthyroidism, hyperparathyroidism, acromegaly, Cushing’s syndrome)

Cafe au lait spots

mutation in a gene called GNAS1 (Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide 1).

64
Q

Mazabraud’s syndrome

A

Fibrous dysplasia associated with intramuscular myxoma

activating mutation in GNAS1

65
Q

syndromes associated with Wilms tumor

A

Beckwith-Wiedeman

WAGR

Denys-Drash

Trisomy 18

Hemihypertrophy

Congenital aniridia

66
Q

Beckwith-Wiedemann syndrome

A

macroglossia, gigantism, umbilical hernia

hepatoblastoma?

67
Q

WAGR

A

Wilms’ tumor

Aniridia

Genitourinary malformations

mental Retardation

68
Q

Denys-Drash syndrome

A

Wilms tumor

pseudohermaphroditism

glomerulopathy

69
Q

Polyglandular autoimmune syndrome I

A

at least 2 of the following:

Addison’s disease

hypoparathyroidism

chronic mucocutaneous candidiasis

70
Q

Polyglandular autoimmune syndrome II

A

Addison’s disease

autoimmune thyroid disease

insulin-dependent diabetes mellitus

71
Q

familial disorders associated with pheochromocytoma

A

MEN 2A, MEN
2B, von Hippel-Lindau disease,
Neurofibromatosis Type 1, Sturge-
Weber disease, hereditary
paraganglioma syndromes.

72
Q

carney syndrome

A

acromegaly

pituitary gigantism

hypercortisolism

sexual precocity

spotty mucocutaneous hyperpigmentation

regulatory subunit 1A of protein kinase A (PRKAR1A) located at 17q22-24

73
Q

Sturge-Weber syndrome

A

aka “encephalotrigeminal angiomatosis”

rare congenital neurological and skin disorder

one of the phakomatoses (neurocutaneous syndromes: NF, TS, AT, VHL, IP, nevoid BCC synd)

port-wine stains of the face, glaucoma, seizures, mental retardation, and ipsilateral leptomeningeal angioma

It is characterized by abnormal blood vessels on the brain surface. Normally, only one side of the brain is affected.

Sturge-Weber is an embryonal developmental anomaly resulting from errors in mesodermal and ectodermal development. Unlike other neurocutaneous disorders (phakomatoses), Sturge-Weber occurs sporadically (i.e., does not have a hereditary etiology).

74
Q

Brooke-Spiegler syndrome

A

Multiple familial trichoepithelioma

autosomal dominant

predisposition to develop cutaneous adnexal neoplasms such as cylindromas, trichoepitheliomas, spiradenomas, trichoblastomas, basal-cell carcinomas, follicular cysts, organoid nevi, and malignant transformation of pre-existing tumors

F > M

CYLD tumor-suppressor gene