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Adrenogenital Syndrome
Clinical: Masculinization in women, feminization in men and precocious puberty in children
Pathophysiology: Adrenal virilism realted to enzymatic defects in biosynthesis of cortical steroids leading to
cortisol deficiency: at least 8 distinctive syndromes including 21-hydroxylase deficiency, 11-hydroxylase deficiency
Micro: Adrenocortical hyperplasia
Adrenoleukodystrophy
Clinical: Onset later than other leukodystrophies (Metachromatic and Krabbe's Disease). Males ages 10-20,
Females 20-40.
Presents with adrenal failure and segmental demyelinization and axonal degeneration of CNS.
Transmission: X linked recesive
Pathophysiology: Defect in fatty acyl-coenzyme A ligase (a peroxismal transporter enzyme) leads to accumulation
of long-chain fatty esters of cholesterol.
EM: Cytoplasmic inclusions of dense, long, thin leaflets enclosing an electron-lucent space in cerebral
macrophages, adrenocortical cells, testicular Leydig cells and Schwann cells
Alagille's Syndrome
AKA: Arterio-hepatic dysplasia
Clinical: Broad facies, hypertelorism, short stature, butterfly vertebrae, mental retardation, hypogonadism,
pulmonary artery stenosis
Transmission: AD, association with Trisomy 21, 18, 17; 45XO
Cytogenetics: Mutation in gene Jagged1 on chromosome 20p, encodes ligand for Notch1, which plays a role in
epithelial-mesenchymal interactions
Micro: Congenital absence of intrahepatic bile ducts, portal tract fibrosis, neonatal giant cell hepatitis
Albers-Schnberg Disease
AKA: Osteopetrosis, Marble-bone disease
Clinical: Malignant AR form evident in utero or soon after birth: fractures, anemia, hydrocephaly, cranial nerve
problems (optic atrophy, deafness, facial paralysis), repeated infections, HSM (from extramedullary hematopoiesis).
AD benign adult form usually detected in adolesence or adulthood on X-rays of repeated fractures. Milder cranial
nerve deficits and anemia.
Transmission: Malignant AR evident in utero or infancy; AD adult form has a benign course
Pathophysiology: Carbonic anhydrase II deficiency required by osteoclasts and renal tubular cells to acidify their
environment; osteoclasts can't generate superoxide.
Diagnosis: Radiographic features characteristic: diffuse sclerosis and distal metaphyses misshapen
Gross: Overgrowth and sclerosis of bone with marked thickening of cortex and narrowing/filling of medullary
cavity. Ends of long bones are bulbous (Erlenmyer flask deformity) and misshapen. The neural formamina are small
and compress existing nerves.
Micro: Spongiosa persists and there is no room for hematopoetic marrow. Bone that forms is not remodeled,
remains woven.
Treatment: Some benefit from IFN-g, bone marrow transplant.
Albright's Syndrome
AKA: McCune-Albright Syndrome
Alkaptonuria
AKA: Ochronosis
Alport's Syndrome
Mneumonic: NEDH
Clinical: Nephrotic syndrome, Eye abnormalities (lens dislocation, posterior cataracts, corneal dystrophy), nerve
Deafness, Hematuria. Males are affected more frequently and more likely to progress. Symptoms appear between
ages 5 and 20 usually with microscopic hematuria. Renal failure occurs by age 20-50 in med. Auditory defects may
be subtle.
Pathophysiology: Defective GBM synthesis due to mutations in a5 chain of collagen IV (COL4A5 gene), X linked
form associated with diffuse leiomyomatosis has additional mutations in a6 chain. AR transmission associated with
mutations in a3 and a4 chains.
Diagnosis: Skin biopsy also shows lack of a5 collagen staining
Transmission: Most X-linked, Xq22, but AR and AD pedigrees exist
Micro: Early lesion: segmental proliferation or sclerosis with an increase in mesangial matrix and persistence of
fetal-like glomeruli. Later: tubular epithelial foam cells and increasing glomerulosclerosis.
EM: GBM shows irregular thickening and thinning with splitting of lamina densa
Stains: Antibodies to a3, a4, and a5 collagen fail to stain both glomerular and tubulat basement membranes
Angelman Syndrome
Clinical: "Happy puppets": mental retardation, ataxic gait, seizures, inappropriate laughter
Cytogenetics: Maternal imprinting of chromosome 15; del(15)(q11q13)
Arnold-Chiari Malformation
Mneumonic: CHASM (Cerebellum protrudes, Hydrocephalus, Spinal dysraphism, Medulla kinked)
Pathophysiology: Disproportionate growth of posterior fossa
Gross:
Type I: benign cerebellar tonsillar herniation
Type II: small posterior fossa with extreme cerebellar tonsillar herniation through foramen magnum, kinked cervical
spinal cord, tegmental beaking, lumbosacral meningomyelocele, 80% hydrocephalus
Asherman's Syndrome
Mneumonic: AAA
Clinical: infertility (Abortions), Adhesions, Amenorrhea, associated with excessive dilatation and curettage (D&C).
Gross: endometrial synechiae
Ataxia Telangiectasia
AKA: AT
Clinical: cerebellar ataxia, immunodeficiency, sensitivity to ionizing radiation, lymphoid malignancies
Increased risk of NHL, leukemia, brain tumors, gastric cancer, breast cancer (11% chance by age 50 in
heterozygotes)
Transmission: AR; 1% of population is a carrier
Pathophysiology: AT protein (ATM gene) is a sensor of DNA damage; absence leads to defective DNA repair and
accelerated cell aging
Micro: Gradual loss of Purkinje cells in the cerebellum
Banti Syndrome
Clinical:recanalization of an ectatic portal vein and associated splenomegaly, anemia, splenic vein thrombosis;
usually occurs years after an occlussive event (e.g. neonatal omphalitis or umbilical vein catheterization).
Bartonellosis
AKA: Carrion's Disease
Clinical: Acute febrile fever (oroya fever) associated with hemolytic anemia and hepatosplenomegaly followed by
nodular, inflammatory lesions consisting of inflammatory cells
Pathophysiology: Bartonella bacilliformis, carried by sandfly vector
Bartter's Syndrome
Clinical: Polyuria with K+ wasting and metabolic alkalosis
Pathophysiology: Secondary hyperaldosteronism from renin overproduction
Diagnosis: Hyperreninemia, Hyperaldosteronemia, Hypokalemia, Metabolic alkalosis, serum HCO3, urine ClMicro: Juxtaglomerular cell hyperplasia
Bechet's Disease
Mneumonic: CAVE (CNS, Apthous ulcers/Autoimmune, Vasculitis/Venous thrombosis, Eye
Clinical: young males with hypopyon, uveitis, iridocyclitis, oral/genital aphthous ulcers, arthritis, inflammatory
bowel disease
Pathophysiology: immune complex mediated, leukocytoclastic vasculitis
Treatment: Chlorambucil
Beckwith-Wiedemann Syndrome
Clinical: macrosomia, macroglossia, exopthalmos, neonatal hypoglycemia, hemihypertrophy, renal medullary cysts,
adrenal cytomegaly; increased risk of Wilms' tumor, hepatoblastomas, adrenocorticoid tumors, rhabdomyosarcoma,
pancreatic tumors. (see also Denys-Drash Syndrome and WAGR Syndrome for other Wilms' tumor associated
syndromes)
Transmission: AR, gene WT-2 on 11p15.5; uniparental disomy in sporadic cases
Berger's Disease
AKA: IgA nephropathy
Micro: Segmental, diffuse or crescentic glomerulonephritis
IF: IgA deposits in mesangium
Bernard-Soulier Syndrome
Clinical: purpura, epistaxis, gingival bleeding, menorrhagia, hematuria, GI bleeding
Pathophysiology: GPIb/V/IX deficiency on platelet surface; affected platelets can't bind vWF
Transmission: AR
Diagnosis: Normal platelet aggregation with ADP, collagen, epinephrine but lack of aggregation with ristocetin
Micro: Large platelets (2-5x normal), reduced numbers
Binswanger's Disease
AKA: subcortical leukoencephalopathy
Clinical: Hypertensive patients with progressive dementia
Micro: Diffuse loss of deep hemispheric white matter
Bloom Syndrome
Clinical: Leukemia, GI carcinoma
Transmission: AR
Pathophysiology: spontaneous chromatid breakage
Bourneville's Disease
AKA: Tuberous Sclerosis
Bouttonneuse Fever
Clinical: Rickettsial disese in Mediterranean/India, promintn eschar and "tache noire"
Pathophysiology: Rickettsia conorii
Transmission: tick bite
Breakbone Fever
AKA: Dengue Fever
Clinical: gnawing bone pain
Brill-Zinsser Disease
Clinical: Typhus group (no eschar) Rickettsial disease; similar to epidemic typhus but milder
Pathophysiology: Rickettsia prowazekii, late reactivation
Bruton's Agammaglobulinemia
Transmission: X-linked
Pathophysiology: Defective B cell maturation
Diagnosis: Near-total absence of immunoglobulins in serum
Buerger's Disease
AKA: Thromboangiitis obliterans
Clinical: Male smokers
Micro: Thromboangiitis obliterans with segmenta; thrombosing acute and chronic inflammation of intermediate and
small arteries and veins of the extremities.
Byler Disease
Transmission: AR
Pathophysiology: impairment of bile acids and phosphotidylcholine secretion leading to progressive intrahepatic
cholestasis
Byssinosis
Clinical: Pulmonary disorder caused by dust from cotton, flax or hemp. Takes form more like asthmatic bronchitis.
Caisson Disease
AKA: "The bends", decompression sickness
Clinical: Scuba divers
Pathophysiology: Sudden changes in atmospheric pressure cause nitrogen to come out of fluid and the resulting
embolisms lead to multiple foci of ischemic necrosis
Caplan's Syndrome
Clinical: pulmonary rheumatoid arthritis with pneumoconiosis; distinctive nodular pulmonary lesions on CXR that
develop rapidly.
Pathophysiology: Seen in silicosis, asbestosis, other dust-caused pneumoconioses
Micro: pulmonary rheumatoid nodules with central necrosis surrounded by fibroblasts, macrophages, and collagen
in a background of progressive massive fibrosis
Carcinoid Syndrome
Clinical: blushing, flushing, diarrhea, cutaneous angiomas, tricuspid valve and pulmonary valve stenosis, bronchial
spasm
Pathophysiology: serotonin, 5-HIAA release from carcinoid tumors that have metastasized to the liver
Carney's Syndrome
Clinical: cutaneous and soft tissue myxomas, cardiac myxomas, skin pigmentation, adrenal lesions
Carney's Triad
Clinical:
GISTs/leiomyoblastomas
Pulmonay Chondromas
Extra-Adrenal Paragangliomas
Caroli's Disease
Clinical: Congenital intrahepatic biliary dilatation; 25% associated with polycyctic kidney. Increased risk of
cholangiocarcinoma. Often complicated by intrahepatic cholelithiasis, cholangitis, hepatic abscesses and portal
HTN.
Transmission: AR
Micro: communicating cavernous biliary ectasia; may be seen in conjunction with congenital hepatic fibrosis
Carrion's Disease
AKA: Bartonellosis
Castleman's Disease
Clinical: Lymphadenopathy, fever, multiorgan dysfunction
Often seen in patients with POEMS
Diagnosis: Hypergammaglobulinemia
Chaga's Disease
AKA: American trypanosomiasis
Clinical: Myocarditis (America), Megaesophagus and megacolon (Brazil)
Pathophysiology: T. cruzi
Charcot-Buchard Aneurysm
Clinical: microaneurysms that form at bifurcations of small intraparenchymal cerebral arteries (lenticulostriate
arteries) due to hypertension which may rupture and cause spontaneous intracerebral hemorrhages (basal ganglia,
pons, cerebellum)
Charcot-Marie-Tooth Disease
AKA: peroneal muscular atrophy; hereditary sensory motor neuropathy Type I
Clinical: Wasting and weakness of lower leg and foot giving characteristic inverted "champagne bottle limb."
Transmission: AD
Pathophysiology: demyelination
Micro: onion bulb nerves
Chediak-Higashi Syndrome
Mneumonic: CAMP (Chemotaxis, AR, Microtubules, Phagocytosis)
Clinical: Neutropenia, albinism, HSM, lymphadenopathy, nerve defects, bleeding diathesis
Transmission: AR
Pathophysiology: Abnormal PMN peroxidase granules, impaired chemotaxis and phagocytosis from defect in
microtubute polymerization. Reduced transfer or lysosomal enzymes to phagocytic vacuoles, melanocytes, nerves
and platelets.
Diagnosis: Neutrophils have giant granules on peripheral blood smear. Hct, Plt,
Chiari-Frommel Syndrome
Clinical: Post-partum patients in which continued secretion of prolactin from the pituitary inhibits reinstitution of
menstrual cycle.
Micro: Atrophic vaginal smear.
Churg-Strauss Syndrome
Mneumonic: VEGA (Vasculitis, Eosinophilia, Granulomas, Asthma)
AKA: allergic granulomatous angiitis
Clinical: asthma, fever, eosinophilia
Micro: Eosinophil-rich and granulomatous inflammation involving the respiratory tract. Necrotizing vasculitis
affecting small to medium-sized vessels.
Diagnosis: pANCA positive
Cockayne Syndrome
Clinical: Rare disease characterized by premature aging
Pathophysiology: DGenetic instability in somatic cells
Conn's Syndrome
Mneumonic: HANK (Hypertension, Aldosterone/Adenoma, Neuromuscular weakness, K+ wasting) - this has been
on more than one exam
AKA: Primary aldosteronism
Clinical: edema, HTN
65% caused by adenoma, 35% caused by adrenal hyperplasia, <5% caused by cancer
Diagnosis: K, Na, pH, low renin
Costello Syndrome
Clinical: papilloma and benign tumors of ectodermal origin, incidence rhabdomyosarcoma, possibly bladder
carcinoma, mental retardation, short stature, macrocephaly, "coarse" facial features, hoarse voice, and redundant
skin with deep palmar and plantar creases.
Transmission: sporadic dominant mutation, AD or AR
Pathophysiology: decreased elastin gene expression (?)
Cowden's Syndrome
Mneumonic: PATH (Polyp/papilloma of cord, Acral keratosis, Tricholemomas/tumor of breast, Hamartoma)
AKA: Multiple hamartoma syndrome
Clinical: hypertrichosis, gingival fibromatosis, oral mucosal papillomas, breast fibroadenomas, breast cancer (3050% chance by age 50), facial trichilemmomas, small bowel and colonic hamartomatous polyps (non-Peutz
Jegher's), thyroid disease
Transmission: AD
Cytogenetics: Chromosome 10q
CREST
Clinical: Calcinosis cutis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, Telangectasias (a
limited form of scleroderma). Clinical course relatively benign.
Creutzfeld-Jacob Disease
AKA: Subacute spongioform encephalopathy
Clinical: Rapidly progressive dementia, myoclonus, ataxia
Micro: Cortico-striatal-spinal degeneration
Cronkhite-Canada Syndrome
Mneumonic: JAHN (Juvenile polyps, Alopecia, Hyperpigmentation, Nail atrophy)
Clinical: hamartomatous GI polyps, diffuse alopecia, nail dystrophy, hyperpigmentation
Crouzon's Syndrome
AKA: Craniofacial dysostosis
Cushing's Syndrome
AKA: hypercortisolism; Cushing's Disease when caused by a pituitary adenoma.
Clinical: central obesity, moon facies, acne, buffalo hump, hirsutism, amenorrhea, striae, hypertension, mental
status changes
Pathophysiology: adrenocortical secretion of cortisol caused by ACTH levels caused by pituitary adenoma,
neoplasms of the adrenal cortex or ectopic ACTH from a neuroendocrine tumor (bronchogenic CA, malignant
thymoma, islet cell tumor), may be iatrogenic (steroid Rx).
Dandy-Walker Malformation
Pathophysiology: failure of formation of cerebellar vermis
Gross: no room to 4th ventricle, hydrocephalus, polymicrogyria
Denys-Drash Syndrome
Clinical: gonadal dysgenesis (male pseudohermaphroditism) and nephropathy leading to renal failure; increased
risk of Wilms' tumor. (see also WAGR Syndrome and Beckwith-Wiedemann Syndrome for other Wilms' tumor
associated syndromes)
Transmission: AD
Cytogenetics: 11p13 (WT1)
Pathophysiology: negative missense mutation
Dercum's Disease
AKA: adiposis dolorosa
Dermatomyositis
Clinical: autoimmune inflammatory myopathy, commonly associated with Scleroderma, SLE, Sjogren's. Increased
risk of visceral malignancy. (lung, stomach, ovary)
Devic's Disease
Clinical: A variant of Multiple Sclerosis (neuromyelitis optica) in which the typical MS plaques coexist with
necrotic lesions in the spinal cord and demyelination in the optic nerve.
Diamond-Blackfan Anemia
AKA: congenital chronic pure red cell aplasia
Clinical: presents at 2 weeks-1 year
Pathophysiology: Defective erythroid-committed stem cells
Di George Syndrome
Mneumonic: CATCH 22 (Cardiac abnormalities, Abnormal facies, T cell deficit/tetany, Cleft palate,
Hypocalcemia from parathyroid hypoplasia, chromosome 22q11)
AKA: Thymic hypoplasia; 22q11 deletion syndrome (includes velocardiofacial syndrome)
Clinical: Recurrent fungal and viral infections, tetany, risk of squamous cell ca or upper respiratory tract
Patients with partial DiGeorge Syndrome have a small but histologically normal thymus and T cell function
improves with age.
Transmission: AD
Pathophysiology: Failure of third and fourth pharyngeal pouches, loss of T cell mediated immunity
Diagnosis: Low levels of circulating T cells. Deletion 22q11 (90%)
Gross: Absence of thymus, parathyroids, clear cells of thyroid, heart and great vessels (ultimobrachial body)
Di Gugliemo Syndrome
AKA: erythremic myelosis, erythromeloblastic leukemia, AML M6
Down Syndrome
AKA: Trisomy 21
Clinical: flat facial profile, oblique palpebral fissures and epicanthic folds, mental retardation (severe in 80%), 40%
have congenital heart disease (endocardial cushion defects: ostium primum, ASD, AV valve malformations, VSD),
atresias of esophaus and small intestine; risk of acute leukemia (10-20x) ALL & AML; age>40 yo develop
neuropathic changes similar to Alzheimer's disease; abnormal immune responses (lung infections, thyroid
autoimmunity)
Cytogenetics: 95% have trisomy 21; most common cause is meiotic nondisjunction; 95% extra chromosome is
maternal origin;
4% of cases from a robertsonian translocation (familial); 1% are mosaics as a result of mitotic nondisjunction of
chrom 21.
facial, neurologic and cardiovascular changes limited to 21q22.2 and 21q22.3
Prognosis: 80% survive to age 30 or beyond
Dressler's Syndrome
Clinical: Occurs 2-21 weeks s/p MI, cardiac trauma or cardiotomy: fever, pleuritis, pericarditis, pneumonitis,
arthritis, leukocytosis
Pathophysiology: autoimmune pericarditis
Eaton-Lambert Syndrome
AKA: myasthenic syndrome
Clinical: progressive proximal muscle weakness without cranial muscle weakness; associated with oat cell
carcinoma
Diagnosis: action potential with repetitive stimulation
Treatment: Guanidine
Edward's Syndrome
AKA: Trisomy 18
Clinical: overlapping fingers, renal and cardiac anomalies
Eisenmenger's Syndrome
Clinical: reversal of congenital left to right shunt (e.g. ASD, VSD, PDA), pulmonary hypertension, RVH, cyanosis
Evans Syndrome
Clinical: autoimmune thrombocytopenia along with autoimmune hemolytic anemia
Fabry's Disease
AKA: angiokeratoma corporis diffusum universalis
Clinical: purple angiokeratomas on thighs, buttocks and genitalia, anhidrosis, parasthesias in lower extremities;
CNS, cardiac and renal complications
Transmission: X linked Recessive; Xq21-22
Pathophysiology: No a galactosidase sphingolipid (ceramide trihexoside) in histiocytes and vessel walls
Diagnosis: zebra body glomerular deposits
Fanconi Anemia
Clinical: renal hypoplasia, absent or hypoplastic thumbs or radii, skin hyperpigmentation, microcephaly, risk of
AML, squamous carcinoma, hepatocellular carcinoma
Transmission: AR
Pathophysiology: Defective DNA repair mechanism
Fanconi's Syndrome
Mneumonic: KAT (Kidney, Aplastic anemia, Thumbs - absent)
Clinical: acute leukemia, squamous carcinomas & hepatomas, cystinosis, osteomalacia
Transmission: AR
Pathophysiology: 2 to myeloma or poisoning defective renal tubular function
Felty's Syndrome
Mneumonic: SAUL (Splenomegaly, Arthritis, Ulcers (leg), Leukopenia)
Clinical: Rheumatoid arthritis with leg ulcers, splenomegaly with leukopenia & granulocytopenia
Fitz-Hugh-Curtis Syndrome
Clinical: stabbing RUQ abdominal pain
Pathophysiology: perihepatitis caused by spread of untreated gonorrheal cervicitis
Forbes-Albright Syndrome
Clinical: Pituitary chromophobe adenomas or craniopharyngeomas associated with gonadotropins causing
secondary amenorrhea with galactorrhea.
Micro: Atrophic vaginal smear.
Fragile X
Clinical: Mental retardation
Transmission: X linked
Cytogenetics: Xq27.3
Freidrich's Ataxia
Clinical: gait ataxia, hand clumsiness, dysarthria, -DTR, impaired joint position and vibratory sense. +Babinski,
Transmission: AR with male preponderance
Pathophysiology: Unknown
Gross: Small spinal cord
Micro: Loss of nerve fibers and gliosis of posterior columns, distal corticospinal tract, spinocerebellar tracts and
loss of dorsal root ganglion cells.
Gaisbock's Syndrome
Clinical: Stress polycythemia of unknown etiology
Gardner's Syndrome
Mneumonic: DO STOP (Desmoid/AD, Osteomas, Sebaceous cysts, Thyroid cancer/tooth abnormal,
Osteochondromas, Polyps)
Clinical: colonic polyposis with high malignant potential, skull osteomas, soft tissue tumors: calcifying epithelioma
of Malherbe, fibromatosis/desmoid, lipomas, sebaceous cysts, fibromas, fibrosarcomas; dental abnormalities
Gaucher Disease
Clinical: The most common lyssomal storage disorder.
HSM, lymphadenopathy, bone destruction
Type I (99%) non-neuronopathic. Splenic and skeletal involvement, lymphadenopath., European Jews. Reduced but
detectible activity. Longevity mildly shortened.
Type II (<1%) neuronopathic. Infantile acute cerebral. No predeliction for Jews. No detectible activity. HSM and
progressive CNS involvement. Early death.
Type III (<1%) mild neuronal symptoms, "intermediate" usu juveniles wth systemic involvement as in type I but
CNS involvement is in teens or 20s.
Transmission: AR; gene 1q21
Pathophysiology: Absence of glucocerebrosidase (cleaves glucose residue from ceramide); accumulates in
phagocytic cells.
Diagnosis: Glucocerebrocidase activity in peripheral blood leukocytes or in extracts of cultured skin fibroblasts.
Micro: Gaucher cells: distended phagocytic cells, with fibrillary cytoplasm like crumpled tissue paper and dark,
eccentric nuclei. Type I: bone erosion or large, gray tumorous masses. Type II: Gaucher cells in Virchow-Robin
spaces. Neurons appear shrivelled and progressively destroyed.
Stains: PAS+
Gilbert's Disease
AKA: familial non-hemolytic jaundice
Clinical: Benign hereditary disorder, usually asymtomatic or produces a mild jaundice
Transmission: AD?
Pathophysiology: decreased uptake of bilirubin by the hepatocytes, mild deficiencies in UGT (glocoronyl
transferase) and in 50% mild hemolysis
Diagnosis: unconjugated hyperbilirubinemia, especially after fasting
Glantzmann Thrombasthenia
Clinical: Bleeding diasthesis
Pathophysiology: Inactive or deficient GpIIb-IIIa causing defective platelet aggregation
Goodpasture's Syndrome
AKA: Anti-GBM Disease
Clinical: nephritic syndrome/RPGN, pulmonary hemorrhage
Pathophysiology: Anti-glomerular basement membrane antibody
Micro:
Lung - necrotizing, hemorrhagic pneumonia
Kidney - glomerulonephritis
EM: deposits in capillary loops
IF: linear IgG, C3
Gorham's Disease
AKA: massive osteolysis
Clinical: reabsorption of whole or multiple bones and filling of residual spaces with heavily vascularized fibrous
tissue
Gorlin's Syndrome
AKA: Basal Cell Nevus Syndrome
Mneumonic: REBOCK (Reproductive organs, Eyes, Bone, Ca+2 of dura, Keratinous cyst of jaw)
Clinical: multiple basal cell carcinomas, odontogenic cysts of the jaw, defective dentition, rib/vertebral/metacarpal
abnormalities, ovarian fibroids and carcinoma, calcificantion of falx & dura, increased risk of medulloblastoma
Transmission: AD
Graves' Disease
Pathophysiology: hyperthyroidism due to long stimulating thyroid antibodies
Gregg's Syndrome
Mneumonic: PRE MD
AKA: Congenital Rubella Syndrome
Clinical: Patent ductus, Rubella, Eye (cataract), Mental retardation, Deafness
Guillan-Barr Syndrome
Mneumonic: MAD (Motor paralysis, Anti-myelin, Demyelination)
AKA: Acute idiopathic polyneuritis
Clinical: Affects all ages, clidren & adults; mild URI precedes neurologic sx by 1-3 weeks in 50% of cases.
Presents with weakness of proximal and distal limb muscles, trunk muscles, ascending paralysis. Association with
infectious mono, hepatitis, diptheria, porphyria or toxins (triorthocresyl phosphate poisoning, Jamaican ginger)
Pathophysiology: acute demyelinating process
Hamman-Rich Syndrome
Hand-Foot-and-Mouth Disease
Clinical: pearly grey vesicles on fingers, toes, palms, soles, buccal mucosa and tongue
Pathophysiology: Coxsackie A-16
Hansen's Disease
AKA: Leprosy
Clinical: Tuberculoid (TT) and Lepromatous (LL) forms.
TT: Macular skin lesions with prominent nerve involvement (ulnar and peroneal) leading to skin anesthesia, muscle
atrophy and eventually skin ulcers; skin contractures, paralysis, autoamputation of fingers and toes.
LL: Nodular lesions (skin, peripheral nerves, anterior eye, upper airways to larynx, testes, hands, feet) may result in
sensory imapirment and "Leonine facies."
Transmission: TT form is not contagious.
Pathophysiology: Mycobacteria leprae
Diagnosis: Acid fast obligate intracellular bacteria
Few organsims in TT; Lots in LL.
Micro:
TT: Garnulomatous lesions with scant organisms
LL: Abundant histiocytes and easily identified organisms
Prognosis: LL more difficult to cure.
Hartnup's Disease
Clinical: Symptoms of pellagra
Pathophysiology: Defective tryptophan transport system leads to decreased nicotinamide
Haverhill Fever
AKA: Rat bite fever
Pathophysiology: Streptobacillus moniliformis
Heerfordt's Syndrome
Clinical: Sarcoidosis, bilateral parotid enlargement, facial nerve palsy, uveitis
HELLP
Clinical: Hemolysis, Elevated Liver function tests, Low Platelets
Pathophysiology: Caused by severe toxemia of pregnancy
Henoch-Schonlein Purpura
Mneumonic: GAAACC (Glomerulonephritis, IgA, Arthralgias, Angiitis, Colic, C3)
Clinical:
Diagnosis: Microsatellite instability can be detected in 15% of sporadic (non-HNPCC) colon cancers
Treatment: Cancer screening
Hermansky-Pudlak Syndrome
Clinical: oculocutaneous albinism, increased ceroid in mononuclear phagocytic system, dense granule deficiency in
platelets
Hirschprung's Disease
Clinical: Congenital megacolon
Pathophysiology: Failure of development of Meissner's and Auerbach's plexuses.
Micro: Ganglion cells are absent at anorectal junction. Nerves hypertrophied.
Horner's Syndrome
Clinical: ptosis, miosis, anhydrosis
Pathophysiology: lesion in sympathetic chain
Horton's Disease
AKA: Temporal (giant cell) arteritis
Hunter Syndrome
AKA: Type II mucopolysaccharidosis
Clinical: Appear normal at birth but develop HSM by 6-24 months. Growth retardation, coarse facial features,
skeletal deformities. Compared to Hurler no corneal clouding and milder clinical course.
Pathophysiology: Deficiency of L-iduronosulfate sulfatase leading to accumulation of heparan sulfate and
dermatan sulfate.
Transmission: X-linked recessive
Hurler Syndrome
AKA: Type I mucopolysaccharidosis
Clinical: Appear normal at birth but develop HSM by 6-24 months. Growth retardation, corneal clouding, coarse
facial features, skeletal deformities. Death by 6-10 years from cardiovascular complications.
Pathophysiology: Deficiency of a-1-iduronidase leading to accumulation of heparan sulfate and dermatan sulfate.
Transmission: AR
Ivemark's Syndrome
Clinical: splenic agenesis, cardiac malformations
Jodbasedow Disease
Clinical: excess iodine ingestion in patients with thyroid disorders causing thyroid toxicosis..
Pathophysiology: Unknown.
Kartagener's Syndrome
Mneumonic: SIBS (Situs inversus, Immotile cilia/infertile male, Bronchiectasis, Sinusitis)
Clinical: complete situs inversus, chronic sinusitis, bronchiectasis, spleen, infertility
Pathophysiology: defect in protein dynein; congenital absence of cilia
Kasabach-Marritt Syndrome
Pathophysiology: giant cavernous hemangioma leading to consumptive thrombocytopenia
Kawasaki's Disease
AKA: Mucocutaneous LN Syndrome
Clinical: conjunctivitis, pharyngitis, cervical lymphadenopathy, peri-vasculitis/vasculitis, finger and toe
desquamation
Kearns-Sayre Syndrome
Mnemonic: MOHR
Clinical: Mitochondrial myopathy resulting in Opthalmoplegia, Heart block & Retinal pigmentary degeneration
Kimmelstiel-Wilson Disease
AKA: Diabetic nephropathy
Clinical: Diabetes mellitus, hypertension, nephrotic syndrome
Klinefelter's Syndrome
Cytogenetics: XXY
Clinical: 1/850 male live births: hypogonadism (atrophic testis, small penis), eunochoid body, lack of secondary
sexual characteristics (deep voice, beard) increased risk of breast cancer.
Diagnosis: Increased FSH
Klippel-Trenaunay-Weber Syndrome
AKA: angio-osteohypertrophy
Clinical: possible increased risk of Wilms tumor
Pathophysiology: angiomatosis underlying bone abnormal, may localized gigantism
Koenig Syndrome
AKA: Cecal tuberculosis
Clinical: alternating constipation and diarrhea, colic, meteorism, gurgling in RLQ
Krabbe's Disease
AKA: Globoid cell leukodystrophy
Clinical: Lysosomal storage disease (sphingolipidosis). Manifests in early childhood as a symmetrical, global
disorder or myelinization which leads rapidly to death before age 2.
Transmission: AR
Pathophysiology: Galactocerebrosidase b-galactosidasedeficiency leading to accumulation of galactocerebrocide
Micro: Demyelination and multinucleated histiocytic cells called globoid cells
Lambert-Eaton Syndrome
Mneumonic: MS eats lambs
Clinical: Myasthenic syndrome associated with malignancy (usually Small cell carcinoma of the lung)
Lawrence-Moon-Biedel Syndrome
AKA: Lawrence-Moon Syndrome
Clinical: retinitis pigmentosa, extra digits, pelvic girdle obsesity, no genital development at puberty, mental
retardation, spastic paraperesis
Transmission: AR
Leigh's Syndrome
AKA: Subacute necrotizing encephalomyelopathy
Clinical: Bilateral, symmetrical regions of necrosis in thalamus, midbrain, pons, medulla and spinal cord resulting
in ataxia, hypotonia, seizures, intellectual deterioration and death.
Transmission: AR
Lesch-Nyhan Syndrome
Clinical: hyperuricemia with uric acid stones, mental retardation, choreoarthetosis, spastic cerebral palsy, selfmutilation
Transmission: X-linked recessive
Pathophysiology: deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) of purine metabolism
Leser-Trelat Syndrome
Clinical: Multiple seborrheic keratoses and internal malignancy
Letterer-Siwe Disease
Mnemonic: Let's See HOPE (Letterer Siwe, HSM, Osteolytic bone lesions, Pumonary lesions, Enlarged LN) for
these poor kids
AKA: Acute disseminated Langerhans Cell Histiocytosis
Clinical: < 2 years old and sometimes present at birth; cutaneous lesions (diffuse maculopapular, eczematous or
purpuric) on trunk and scalp, hepatosplenomegaly, lymphadenopathy, pulmonary lesions, destructive osteolytic bone
lesions.
EM: Rod shaped inclusions in Langerhans cells (Birbeck granules)
Prognosis: poor (aggressive course), untreated disease is uniformly fatal. With chemoRx 5 year survival is 50%.
Liddle Syndrome
Clinical: Salt-sensitive hypertension
Pathophysiology: Mutation in epithelial sodium channel protein lead to increased distal tubular sodium reabsoption
Libman-Sacks Endocarditis
Clinical: Noninfective verrucous endocarditis attributable to elevated levels of circulating immune complexes
occuring in patients with SLE.
Li-Fraumeni Syndrome
Clinical: Multiple sarcomas and carcinomas (breast carcinoma, adrenal cortex), leukemia and brain tumors; 25-fold
greater chance of developing a carcinoma by age 50 than general population. Develop in young age and develop
multiple primaries.
Cytogenetics: Germ line mutations of p53 (17p13.1) - cell cycle regulator, G1 arrest of DNA damaged cells
Leffler's Syndrome
Clinical: eosinophilic pneumonia with granulomas; usually self-limited
Lofgen's Syndrome
Clinical: fever, erythema nodosum (lower extremities), possible sarcoid
Lutembacher's Syndrome
Clinical: Rheumatic mitral valve stenosis and ASD leading to pulmonary HTN from increased left sided pressure.
Maffucci's Syndrome
AKA: dyschondroplasia with vascular hamartomas
Clinical: multiple cavernous hemangiomas (skin) and enchondromas
Marek's Disease
Clinical: Herpes virus infection contracted from fowl causing neuro lymphomatosis
Marie-Strumpell Disease
AKA: Ankylosing spondylitis, Rheumatoid spondalitis
Clinical: Arthritis of sacroiliac joints and vertebral columns in young men.
Cytogenetics: Association with HLA B-27
Marfan Syndrome
Clinical: 1 in 10,000-20,000; 70-85% familial
arachnodactyly, dolichocephalic (long head), lax joints, bilateral ectopia lentis, aortic aneurysms/dissections/ valve
incompetence, mitral valve prolapse/regurge, spinal deformities (kyphosis, scoliosis), skeletal abnormalities (pectus
excavatum or pigeon-breast)
Transmission: AD or sporadic
Pathophysiology: Mutation in fibrillin 1(major component of extracellular matrix) leads to defect in connective
tissue integrity. In heterozygotes mutant fibrillin disrupts the assembly of normal microfibrils (dominant negative
mutation).
Diagnosis: Direct gene diagnosis is not feasible. Presymtomatic detection by RFLP analysis.
Cytogenetics: FBN1 in 15q21.1; great interfamilial variability/expressivity
Micro: Aortic cystic medial necrosis
Prognosis: Aortic rupture is the cause of death in 30-45%, other deaths from cardiac failure.
McArdle Disease
AKA: Type V glycogenosis
Clinical: Congenital myopathy with onset in adulthood (>20 yo) presents with muscle cramps after exercise and
failure of exercise-induced rise in blood lactate due to block in glycolysis. 50% myoglobinuria.
Pathophysiology: Myophosphorylase deficiency
Micro: Glycogen accumulations in skeletal muscle only in subsarcolemmal location
McCune-Albright Syndrome
AKA: Albright Syndrome
Mneumonic: CAFE
Clinical: Cafe-au-lait spots with irregular serpiginous borders on neck, chest, back, shouder and pelvis, polyostotic
Fibrous dysplasia (femur>skull>tibia>jaw>humerus), Endocrine -- precocious puberty (females), endocrine
dysfunction (hyperthyroidism, primary adrenal hyperplasia, GH secreting pituitary adenoma)
Pathophysiology: Somatic (not hereditary mutation) involving a guanine nucleotide binding protein leading to
excess cAMP
Meig's Syndrome
Clinical: ovarian fibroma with ipsilateral hydrothorax or ascites
Menetrier's Disease
Clinical: 4th-6th decades. Hypertrophic gastropathy; protein-losing enteropathy; ZES
Pathophysiology: Idiopathic
Gross: Giant cerebriform enlargement of the rugal folds of the gastric mucosa
Micro: Hyperplasia of surface mucus cells; gastric secretions have excessive mucus and little or no HCl
Meniere's Disease
Clinical: inner ear abnormalities, tinnitus, hearing loss, vertigo, N/V, nystagmus
Menkes' Syndrome
Clinical: short, sparse, kinky, hypopigmented hair; Mental retardation with CNS deterioration
Transmission: X linked Recessive
Pathophysiology: disorder of intestinal copper absorption, needed by lysyl-oxidase, resulting in changes in aortic
collagen and elastin
Metachromatic Leukodystrophy
Clinical: Presents in late infancy with progressive motor impairment with mental deterioration. Congenital, juvenile
and adulr presentations occur.
Transmission: AR
Pathophysiology: Deficiency in arylsulfatase A (cerebroside sulfatase)
Diagnosis: Decreased urinary arylsulfatase A.
Mikulicz's Disease
AKA: Used to refer to Sjgren's Syndrome; now refers to any swelling of lacrimal and salivary gland.
Pathophysiology: Lacrimal and salivary gland swelling secondary to lymphoid infiltrate, sarcoidosis, leukemia,
lymphoma or tumors
Milroy's Disease
AKA: heredofamilial congenital lymphedema
Mitsuda Reaction
Clinical: Skin reaction to lepromin occuring 3-4 weeks after injection
Morquio's Syndrome
AKA: type IV mucopolysaccharidosis
Muir-Torre Syndrome
Clinical: multiple sebaceous gland tumors; visceral malignancy
Nelson's Syndrome
Clinical: hyperpigmentation, Cranial nerve III damage (opthalmoplegia), skin pigmentation
Pathophysiology: post-adrenalectomy hyperplasia of the pituitary gland (corticotroph cells)
Diagnosis: ACTH
Neurofibromatosis I (NF I)
AKA: "Peripheral" NF, Von Recklinghausen's Disease
Clinical: 1 in 3000. Multiple neurofibromas, plexiform neurofibromas, caf au lait spots (90%: 6 or more spots >1.5
cm in diameter), Lisch nodules (pigmented iris hamartomas: 94% over age 6, usu asymtomatic), meningiomas, optic
gliomas, 50% skel abnl (erosive defects, scoliosis & bone cysts, tibial pseudoarthrosis)..
Plexiform NF become maligfnant in 5%.
risk (2-4x) of pheochromocytomas, Wilms tumor, AML, rhabdomyosarcoma, optic gliomas, meningiomas. Children
at risk of CML
Transmission: 50% AD, remainder new mutations.
Cytogenetics: 17q11.2 (neurofibromin gene) - tumor suppressor gene, downregulates p21 ras. Penetrance 100% but
expressivity variable.
Micro: Neurofibromas are loose proliferation of neurites, Schwann cells and fibroblasts in a myxoid stroma.
Nezelof's Syndrome
Clinical: absent thymus and cell mediated immunity (like DiGeorge) but with normal parathyroids
Diagnosis: IgG is normal or increased but there is a selective deficiency of isotypes
Niemann-Pick Disease
Clinical: Clinically, biochemically and genetically heterogeneous. risk in Ashkenazi Jewish community.
Type A is severe infantile form (no sphingomyelinase) with severe neurologic impairment and death within first 3
years of life
Type B: hepatosplenomegaly, lymphadenopathy, marrow disease, late or no CNS involvement; survive into
adulthood.
Transmission: AR
Pathophysiology: Lysosomal strorage disease (no sphingomyelinase leading to sphingomyelin accumulation)
Diagnosis: Liver or bone marrow biopsy assays for sphingomyelinase activity.
Gross: Massive splenomegaly; neuronal involvement is diffuse.
Micro: Lipid-laden phagocytic foam cells in spleen, liver, lymph nodes, bone marrow, tonsils, GI tract, lungs.
Stains: Vacuoles stain for fat with Sudan Black and Oil red O.
EM: Lysosomes contain membranous cytoplasmic bodies resenbling concentric lamellated myelin figures, or
parallel palisaded lamella called Zebra bodies
Noonan's Syndrome
AKA: Male Turner's Syndrome, Ullrich-Turner's Syndrome
Clinical: Phenotype of Turner's Syndrome (webbed neck, ptosis, hypogonadism, congenital heart disease and short
stature) without gonadal dysgenesis.
Ochronosis
AKA: Alkaptonuria
Clinical: Blue-black pigmentation in ears, nose and cheeks. Pigment in articular cartilages of the joints. Cartilage
brittle and fibrillated, especially in vertebral column, knees, shoulders and hips, leading to a degenerative
arthropathy.
Transmission: AR
Pathophysiology: Lack of homogentisic oxidase: defect in metabolism of phenylalanine-tyrosine with buildup of
homogentisic acid. Homogentisic acid binds to collagen in connective tissue, tndons and cartilage.
Cytogenetics: 3q21
Diagnosis: Urine turns black due to oxidation
Oculoglandular Syndrome
AKA: Parinaud's Syndrome
Ollier's Disease
Clinical: Non-hereditary. Multiple unilateral enchondromas; often associated with ovarian sex cord-stromal tumors
Osler-Weber-Rendu
AKA: Hereditary hemorrhagic telangiectasia
Clinical: Telangiectasias of face and oral mucosa, respiratory, GI, urinary tracts, CNS, liver, and spleen
Transmission: AD
Pathophysiology: mutations in two TGF-b binding proteins, including the endothelial protein endoglin
arterial blood is shunted into postcapillary venules
Pancoast Syndrome
Parinaud's Syndrome
AKA: Oculoglandular syndrome
Clinical: swelling of the eye, jaw and high cervical lymph nodes caused by cat-scratch disease
Pathophysiology: Bartonella henselae
Patau Syndrome
AKA: Trisomy 13
Patterson-Kelly Syndrome
AKA:Plummer-Vinson Syndrome
Clinical: atrophic glossitis, microcytic hypochromic anemia (Fe deficiency), esophageal webs with dysphagia
Peutz-Jegher's Syndrome
Clinical: melanin spots on lips, buccal mucosa, genitalia and palmar surface of hands; multiple jejunal
hamartomatous polyps with low malignant potential; risk SCTAT, adenoma malignum, mucinous ovarian tumors,
large cell calcifying Sertoli cell tumor
Transmission: AD
Peyronie's Disease
AKA: Penile fibromatosis
Pick's Disease
AKA: Frontotemporal dementia
Clinical: Cerebral dementia
Gross: "Walnut brain"
Pickwickian Syndrome
AKA: Obesity hypoventilation syndrome
Clinical: Hypersomnolence leading to apnea, polycythemia and right sided heart failure.
Plummer-Vinson Syndrome
AKA:Paterson-Kelly Syndrome
Clinical: atrophic glossitis, microcytic hypochromic anemia, esophageal webs with dysphagia
POEMS
Clinical: Polyneuropathy, Organomegaly, Endocrinopathy, M-protein spike, Skin changes
Pompe Disease
AKA: Glycogenosis Type II
Clinical: Cardiomegaly prominent; deposition in all organs with mild hepatomegaly, muscle hypotonia and
cardioresperatory failure in 2 years. Milder adult form with only skeletal muscle chronic myopathy.
Pathophysiology: Lysosomal storage disease: deficiency of a-1-4-glucosidase(acid maltase) resulting in
accumulation of glycogen in lysosomes
Micro: glycogen accumulations lead to ballooning of lysosomes in hepatocytes: lacy cytoplasmic pattern. Glycogen
membrane-bound and sarcolemmal in heart & skel muscle.
Pott's Disease
AKA: Tuberculous spondylitis, Vertebral tuberculosis
Prader-Willi Syndrome
Clinical: mental retardation, short stature, hypotonia, obesity, small hands and feet, hypogonadism
Cytogenetics: Paternal imprinting of chromosome 15; del(15)(q11q13)
Mnemonic: father Willi is fat while mom's a happy Angel (maternal imprinting of chr 15 causes Angelman's
Syndrome)
Ramsay-Hunt Syndrome
Clinical: Facial paralysis
Pathophysiology: VZV infection of geniculate nucleus
Raynaud's Disease
Clinical: Raynaud's phenomenon occuring in the absence of an anatomic lesion in the vessel walls
Raynaud's Phenomenon
Clinical: pain and pallor/cyanosis of distal extremities in response to cold
Pathophysiology: vasoconstriction
Refsum's Disease
Clinical: Hypertrophic neuropathy associated with increased levels of phytanic acid
Reiter's Syndrome
Clinical: Triad of conjunctivitis, non-gonococcal urethritis, arthritis
Cytogenetics: Associated with HLA B-27
Reye's Syndrome
Clinical: history of aspirin ingestion in children for a viral URI; presents with encephalopathy and liver failure.
Micro: Liver shows microvesicular fatty change without coagulative necrosis or inflammation; brain shows global
edema and ischemic changes but no inflammation.
EM: mitochondrial swelling, irregularity and loss of cristae
Riedel's Disease
AKA: Riedel's Thyroiditis
Clinical: Inflammatory fibrosing process of the neck that happens to involve the thyroid.
Pathophysiology: Probably autoimmune, l light chains > k, increased IgA plasma cells
Micro: Keloid-like fibrosis with associated lymphs and plasma cells.
Rotor Syndrome
Clinical: Asymptomatic conjugated hyperbilirubinemia but the liver is not pigmented (in contrast to Dubin Johnson
Syndrome)
Pathophysiology: Secretion of bile into bile canaliculus is impaired.
Sandhoff Disease
Pathophysiology: Lysosomal storage disease, sphingolipidosis; deficiency of hexosaminadase A & B resulting in
accumulation of GM2 ganglioside and globoside
Sanfilippo's Syndrome
AKA: type III mucopolysaccharidosis
Clinical: Types A, B, C, D
Pathophysiology: Deficiency of heparin N-sulfatase leading to accumulation of heparan sulfate.
Transmission: AR
Schmidt's Syndrome
AKA: type II autoimmune Addison's disease
Clinical: Addison's disease, autoimmune thyroid disease and/or IDDM (without hypoparathyroidism or candidiasis)
Sezary Syndrome
AKA: T cell lymphoma/Mycosis fungoides
Clinical: Generalized exfoliative erythroderma but rarely proceeds to tumefacation.
Micro: Leukemia with Sezary (cerebriform T) cells
Stains: CD4+, CD2+, CD7-
Sheehan's Syndrome
Clinical: post-partum pituitary necrosis and infarction; may also occur ouside the setting of pregnancy or in males.
Shy-Drager's Syndrome
Clinical: progressive encephalo-myelopathy, autonomic dysfunction, low BP, impotence, incontinence, anhidrosis,
external opthalmoparesis, muscle tremor and wasting (Parkinsonian)
Pathophysiology: Idiopathic
Sicca Syndrome
Clinical: Sjgren's syndrome occuring without another autoimmune disorder (like rheumatoid arthritis)
Sipple's Syndrome
AKA: MEN IIa
Sjgren's Syndrome
Clinical: dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia) caries, bilateral lacrimal and parotid
enlargement, rheumatoid arthritis, Raynaud's phenomena, facial telangectasias, increased risk of lymphoid
malignancy (40 x)
Pathophysiology: autoimmune destruction of lacrimal and salivary glands
Primary Sjgren's associated with HLA-DR3 and has organ involvement:
e.g. lung - recurrent infections, interstitial fibrosis, GI - angular cheilitis, beefy red tongue, hepatomegaly and PBC;
kidney - RTA, interstitial nephritis;
Secondary Sjgren's associated with HLA-DR4 and is limited to lacrimal/salivary glands
Diagnosis: Antibodies to SS-A (Ro) and SS-B (La); Schirmer's test - absorptive paper to eyes
Micro: Renal involvement is tubulointerstitial nephritis (not glomerular as in SLE or Scleroderma)
Stein-Leventhal Syndrome
AKA: Polycystic ovaries
Clinical: hirsutism, obesity, amenorrhea, infertility, risk for endometrial carcinoma
Diagnosis: excess LHRH LH estrogens, androgens
Gross: large ovaries with thickened tunica albuginea and evenly distributed cysts
Micro: Vaginal smears show intermediate to superficial cell maturation.
Stevens-Johnson Syndrome
Clinical: severe form of erythema multiformemore common in children with mucosal involvement (hemorrhagic
crusts involving lips and mucosa, conjunctiva, urethra, genital or perianal areas), high fever
Stewart-Treves Syndrome
Clinical: post-mastectomy lymphedema of the arm angiosarcoma
Still's Disease
AKA: Juvenile rheumatoid arthritis
Sturge-Weber Syndrome
AKA: Encephalotrigeminal angiomatosis
Clinical: Port wine stain (nevus flamus) in the area of the trigeminal nerve, venous angiomas of leptomeninges,
retina and cortex, associated mental retardation, seizures, hemiplegia and radiopacities of the skull (intracranial
calcifications); choroid angioma glaucoma (any 2 fulfill criteria), pheochromocytomas
Pathophysiology: faulty development of mesodermal and ectodermal elements
function, anemia, leukopenia, thrombocytopenia. Avoid oral BCP because they worsen SLE symptoms. IUDs are
associated with recurrent pelvic infections.
Pathophysiology: Drug-induced (anti-histone Ab positive): hydralazine, procainamide, penicillamine, INH,
phenytoin
Diagnosis: ANA, anti-ds DNA, anti-histone, anti-Sm, SS-A (Ro)
Micro: Hematoxylin bodies - LE cell; fibrinoid necrosis, onionskin lesions
IF: Skin: immunoglobin deposition in dermo-epidermal junction of normal-appearing as well as clinically involved
skin
Cytogenetics: Associations with HLA-DR2 and HLA-DR3 (deletion of C4a gene)
Tangier Disease
Clinical: large orange tonsils, hypolipedemia, corneal opacities, neuropathy, splenomegaly
Pathophysiology: HLA deficiency
Transmission: AR
TaR Syndrome
Clinical: thrombocytopenia, absent radius, congenital heart or renal abnormalities
Transmission: AR
Tay-Sachs Disease
AKA: GM2 Gangliosidosis, Hemoaminidase a-Subunit Deficiency
Clinical: Easter European (Ashkenazi) Jews. Carrier rate 1 in 30. Present at age 6 months: motor incoordination,
mental obtundation leading to muscular flaccidity, blindness and dementia. Death by age 2-3 years.
Transmission: AR
Pathophysiology: Deficiency of hexoaminidase A causes inability to catabolize GM2 Gangliosides
Diagnosis: Retina cherry-red spot.
Micro: Neurins in CNS and autonomic nervous system.
Stains: Oil red O, Sudan Black positive.
EM: Cytoplasmic inclusions: whorled configurations within lysosomes (onio-skin)
Cytogenetics: Chromosome 15, mutations in a subunit locus
Torre's Syndrome
Clinical: multiple sebaceous neoplasms and internal malignancy
Trousseau's Syndrome
Clinical: migratory thrombophlebitis seen in patients with a malignancy (pancreatic carcinoma)
Tuberous Sclerosis
Mneumonic: THAT'S TS (Tubers, Hamartomas, Angiomyolipomas/Angiofibromas/Adenoma Sebaceum, reTinal
tumors, Shagreen skin, hearT rhabdomyoma, Subungal/Seizures)
AKA: Bourneville's Disease
Clinical: cortical hamartomas/tubers (mental retardation, seizures, epilepsy), cutaneous hamartomas
(angiofibromas, sebaceous adenomas), retinal phakomas (fibromas), shagreen skin, ash-leaf hypopigmented
macules, subungal hamartomas, visceral/pancreatic cysts, renal angiomyolipomas (80%; multiple or bilateral),
rhabdomyoma of the heart, increased risk of retinal glial hamartomas and gemistocytic astrocytomas
Transmission: AD with variable expression
Turcot's Syndrome
Clinical: colon adenomatous polyps with high malignant potential & brain tumors (medulloblastoma and fibrillary
astrocytoma)
Transmission: AR
Turner Syndrome
Clinical: shield chest, webbed neck, short stature, cystic hygroma, valgus deformity of elbows, low hair line,
pigmented nevi, risk of atypical polypoid adenomyoma of uterus, aortic coarctation
Cytogenetics: XO, due to nondisjunction of X chromosome, occasionally mosaic
Gross: Ovarian agenesis
Micro: no follicles in ovary (menopause before menarche). Atrophic vaginal smear with maturation index 100/0/0
Usher's Syndrome
Clinical: congenital nerve deafness, retinitis pigmentosa
Vagabond's Disease
AKA: Infection with body louse
von Hippel-Lindau
Clinical: hemangioblastomas of the cerbellum, retina or brainstem, hemangiomas and cysts of the pancreas, liver,
kidneys, epididymis and increased risk of renal cell carcinoma (60%), pheochromocytomas and testicular
cystadenomas/carcinomas
Transmission: AD, gene on 3p25-26 encodes pVHL a tumor suppressor gene
Pathophysiology: pVHL protein inhibits the elongation step of RNA synthesis by interacting with elongin B and
elongin C
Diagnosis: Polycythemia associated with the hemangioblastoma in 10% of cases (EPO production by tumor)
Treatment: nephrectomy for RCC, laser therapy for retinal hemangioblastomas
Waardenburg Syndrome
Clinical: white forelock, lacrimal punctae, width of root of nose, synophrus (eyebrows grow together), cochlear
deafness,
Transmission: AD: PAX 3
WAGR Syndrome
Clinical: Wilms' tumor, Aniridia, Genital anomalies, mental Retardation
35% chance of developing Wilms' tumor (see also Denys-Drash Syndrome and Beckwith-Wiedemann Syndrome for
other Wilms' tumor associated syndromes)
Transmission: AD, gene WT-1 on 11p13
Pathophysiology: nonsense or frameshift mutation
Waterhouse-Friderichsen's Syndrome
Clinical: Acute adrenocortical insufficiency from sudden hemorrhagic destruction of the adrenals, usually
secondary to meningococcemia
Prognosis: vasomotor collapse and shock death.
Weber-Christian Disease
AKA: Relapsing febrile nodular (lobular) panniculitis
Clinical: Nonvasculitic panniculitis with crops of erythematous plaques or nodules on lower extremities of kids and
adults.
Weil's Disease
Clinical: Severe leptospirosis with jaundice, bleeding and renal failure
Werdnig-Hoffman Disease
AKA: Infantile progressive spinal muscular atrophy
Clinical: congenital hypotonia ("floppy infant"). Death from respiratory failure or aspiration
Transmission: AR
Micro: absence/loss of lower motor neurons from anterior horns of spinal cord and neurogenic muscular atrophy
Wermer Syndrome
AKA: MEN I
Werner's Syndrome
Clinical: Rare disease characterized by premature aging, risk of sarcoma
Pathophysiology: Defective DNA helicase (involved in DNA replication & repair)
Wernicke-Korsakoff Syndrome
AKA: Wernicke's encephalopathy and Korsakoff's psychosis
Clinical:
Transmission:
Pathophysiology: Thiamine (vitamin B12) deficiency
Diagnosis:
Gross: Hemorrhagic lesions in mammillary bodies
Micro:
Whipple's Disease
Clinical: A systemic disease affecting white males in 30's-40's (M:F is 10:1) involving small intestine, skin, CNS,
joints, heart, blood vessels, kidney, lungs, serosal memebranes, lymph nodes, spleen and liver. Presents with
malabsorption, diarrhea and polyarterthritis, obscure CNS complaints, lymphadenopathy and hyperpigmentation of
the skin.
Pathophysiology: Tropheryma whippelii, gram-positive actinomycete
Micro: Small intestinal mucosa laden with distended macrophages in the lamina propria. Villi expansion, mucosal
edema, enlarged mesenteric lymph nodes. Bacilli-laden macrophages can also be found in synovium, brain, heart
valves, etc. but other inflammation is essentially absent.
Stains: Macrophages are PAS positive
EM: Rod-shaped bacilli
Treatment: Antibiotic therapy
Williams Syndrome
Clinical: Idiopathic hypercalcemia of infancy leading to metastatic calcifications
Pathophysiology: Abnormal sensitivity to vitamin D
Wilson's Disease
AKA: Hepatolenticular degeneration
Clinical: Presentation in childhood, rarely before age 6 with acute or chronic liver disease, neuropsychiatric sx
(behavioral changes, psychosis, Parkinson-like). Kayser-Fleisher rings (green-brown deposits in Descemet
membrane between limbus and cornea). Copper deposition occurs in liver, brain, cornea, kidneys, bones, joints and
parathyroids
Transmission: AR
Pathophysiology: Accumulation of toxic levels of copper due to defect in ATP7B gene on chromosome 13,
encoding a transmembrane copper-transporting ATPase. Majority of patients are compound heterozygotes.
Diagnosis: Decreased serum ceruloplasmin, increased hepatic copper (>250 ug/gm dry weight) and urinary copper
excretion.
Micro: Liver can show fatty change, acute or chronic hepatitis leading to cirrhosis; rare massive liver necrosis.Brain
has toxic injury to basal ganglia and putamen with atrophy and cavitation.
Stains: Rhodamine or orecin stain copper (can't be seen on H&E).
Treatment: D-penicillamine chelation therapy
Wiskott-Aldrich Syndrome
AKA: Immunodeficiency with thrombocytopenia and eczema
Clinical: Thrombocytopenia, eczema, recurrent infections; risk of non-Hodgkin's lymphomas
Transmission: X linked recessive
Diagnosis: IgM, Nomal IgG, IgA and IgE; Maps to Xp11.23
Gross: Thymus is morphologically normal
Micro: Depletion of T lymphocytes in the peripheral blood and paracortical lymph nodes
Wolman's Disease
Pathophysiology: Deficiency of acid lipase (lysosomal storage disease) resulting in accumulation of cholesterol
esters and triglycerides
Woolsorter's Disease
Clinical: Anthrax in which a diffuse pneumonia occurs which is characterized by extensive serofibrinous exudation
that may produce total lobar consolidation with paucity of pmns, hemorrhagic necrosis of alveolar septa, and
overwhelming abundance of gram-positive bacteria within the exudate.
Pathophysiology: Bacillus anthracis
Xeroderma Pigmentosum
Clinical: extreme photosensitivity, 2000-fold increased risk of skin cancer in sun-exposed skin, neurologic
abnormalities
Transmission: AR
Pathophysiology: inability to repair UV induced DNA damage
Zellweger's Syndrome
AKA: cerebro-hepato-renal syndrome
Clinical: hypotonia, incomplete myelinization, craniofacial malformations, hepatomegaly with cirrhosis, glomerular
cysts
Transmission: AR?
Zieve's Syndrome
Clinical: alcoholic fatty liver, hypercholesterolemia, hypertriglyceridemia with hemolysis, upper abdominal pain
and fever.
Micro: stomatocytosis on peripheral smear
Zollinger-Ellison Syndrome
Clinical: gastric hyperplasia due to gastrin secreting tumor (pancreatic islet cell tumor)