1
Q
Familial retinoblastoma
A
Ch 13
2
Q
Familial adenomatous polyposis
A
aka familial polyposis coli
5q21
can have desmoid tumors (aggressive fibromatosis)
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
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
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
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
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
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
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)
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
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
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
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.
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
15
Q
Cushing’s syndrome
A
high ACTH, adrenal cortical adenomas
can get small cell lung cancer
16
Q
Pt with adrenal cortical adenoma, excess aldosterone (hypernatriemia, hypokalemia, HTN)
A
Conn’s syndrome
17
Q
Patient with tumor and hypoglycemia
A
fibrosarcoma, solitary fibrous tumor, HCC, insulinoma
overproduction of insulin or insulin-like growth factors
18
Q
Pt has tumor and is polycythemic
A
renal cell carcinoma
cerebellar hemangioblastoma
HCC
leiomyoma
solitary fibrous tumor
19
Q
acanthosis nigrans
A
predispostion to gastric carcinoma, lung carcinoma, uterine carcinoma
20
Q
Pt with skin lesions and acoustic neuromas
A
NF-2!
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
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
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
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)
25
Peutz-Jeghers syndrome
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 B**oards": Pancreas, Adenoma malignum of cervix, Sex cord tumors, Sertoli tumors, Breast
26
Cronkite-Canada syndrome
non-inherited
FAP (hamartomatous polyp[s) with skin and nail changes
27
Fabry's disease
* X-linked recessive sphingolipidosis
* deficiency of **alpha-galactosidase A**
* angiokeratomas, renal insufficiency, cardiac failure
* vacuolated myocytes
* EM: intralysosomal dense lamellae (zebra bodies)
28
Carney's syndrome/complex
* 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**
29
Carney's triad
* Multiple **_P_**ulmonary chondromas (hamartomas)
* extra-adrenal**_ P_**aragangliomas
* **_G_**ISTs of the stomach
*
* Think: **_P_**eter, **_P_**aul, and **_G_**ary
* nonfamilial
30
Tuberous sclerosis complex
* 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
Marfan syndrome
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
POEMS syndrome
Polyneuropathy
Organomegaly
Endocrinopathy
Monoclonal gammopathy
Skin changes
- sometimes seen in pts with multicentric Castleman's disease
33
A1-antitrypsin deficiency
* 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
Dubin-Johnson syndrome
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
Rotor syndrome
Autosomal recessive
Decreased hepatic uptake and storage?
Decreased biliary excretion?
No liver pathology
Clinical course: Innocuous; conjugated hyperbilirubinemia
36
Crigler-Najjar syndrome type I
Autosomal recessive
Absent UGT1A1 (UGT, uridine diphosphate-glucuronyltransferase) activity
No liver pathology
Unconjugated hyperbilirubinemia
Fatal in neonatal period
37
Crigler-Najjar syndrome type II
Autosomal dominant with variable penetrance
Decreased UGT1A1(UGT, uridine diphosphate-glucuronyltransferase) activity
No liver pathology
Clinical: Generally mild, occasional kernicterus
Unconjugated hyperbilirubinemia
38
Gilbert syndrome
Autosomal recessive
Decreased UGT1A1 (UGT, uridine diphosphate-glucuronyltransferase) activity
No liver pathology
Unconjugated hyperbilirubinemia
Innocuous
39
Hemochromatosis
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
Wilson's disease
"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
Hereditary hemorrhagic telangiectasia (HHT)
* 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
Henoch-Schonlein purpura
* #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
* 2. arthritis/arthralgia
* 3. abdominal pain
* 4. 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
osteogenesis imperfecta
44
Deficiencies of platelet dense granules
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
2. 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
Kasabach-Merritt syndrome
aka "hemangioma with thrombocytopenia"
association of vascular tumor with consumptive thrombocytopenia
46
21-hydroxylase deficiency
**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
11-beta-hydroxylase deficiency
**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
3-beta-hydroxysteroid dehydrogenase deficience
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
17-alpha-hydroxylase deficiency
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
Gorlin's syndrome
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
Naxos syndrome
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
Peutz-Jegher syndrome
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
Familial Juvenile Polyposis
Autosomal dominant
SMAD4 or BMPR1A
Hamartomatous polyps
\>50% risk of GI CA
including small bowel
and stomach
54
Cronkhite-Canada
syndrome
no known mutated gene
hamartomatous polyps
Severe disease,
electrolyte imbalance and
protein loss; often fatal,
55
Cowden's disease
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
Familial Adenomatous Polyposis
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
Hamartomatous GI polyposis syndromes
Peutz-Jegher syndrome
Familial juvenile polyposis
Cronkhite-Canada syndrome
Cowden's disease
58
Gardner syndrome
Autosomal dominant
APC gene
Same GI lesions as FAP +
osteomas, epidermoid
cysts. fibromas, and
desmoid tumors
59
Turcot syndrome
66% autosomal dominant
33% autosomal recessive
APC gene
Same GI lesions as FAP + PNET of CNS &
Glioblastoma multiforme
60
Hereditary nonpolyposis colorectal carcinoma (HNPCC)
**_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
Ollier's disease
Multiple enchondromata
62
Maffucci's syndrome
## Footnote
Mutliple enchondromata + angiomata (hemangiomas, lymphangiomas of skin, soft tissue, organs, etc)
also higher incidence of other malignancies, esp soft tissue and GU tract
63
McCune-Albright syndrome
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
Mazabraud's syndrome
Fibrous dysplasia associated with intramuscular myxoma
activating mutation in **GNAS1**
65
syndromes associated with Wilms tumor
Beckwith-Wiedeman
WAGR
Denys-Drash
Trisomy 18
Hemihypertrophy
Congenital aniridia
66
Beckwith-Wiedemann syndrome
macroglossia, gigantism, umbilical hernia
hepatoblastoma?
67
WAGR
Wilms' tumor
Aniridia
Genitourinary malformations
mental Retardation
68
Denys-Drash syndrome
Wilms tumor
pseudohermaphroditism
glomerulopathy
69
Polyglandular autoimmune syndrome I
at least 2 of the following:
Addison's disease
hypoparathyroidism
chronic mucocutaneous candidiasis
70
Polyglandular autoimmune syndrome II
Addison's disease
autoimmune thyroid disease
insulin-dependent diabetes mellitus
71
familial disorders associated with pheochromocytoma
MEN 2A, MEN
2B, von Hippel-Lindau disease,
Neurofibromatosis Type 1, Sturge-
Weber disease, hereditary
paraganglioma syndromes.
72
carney syndrome
acromegaly
pituitary gigantism
hypercortisolism
sexual precocity
spotty mucocutaneous hyperpigmentation
regulatory subunit 1A of protein kinase A (PRKAR1A) located at 17q22-24
73
Sturge-Weber syndrome
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
Brooke-Spiegler syndrome
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
Osler
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