Addison's Disease
AKA: Adrenocortical insufficiency
Clinical: Weakness, fatigueability, weight loss, anorexia, hypotension
Syndromes of multiple autoimmune disorders that include Addison's Disease fall into two subtypes:
· 2/3 of triad of Addison's, hypoparathyroidism and mucocutaneous candidiasis
· Schmidt's Syndrome

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

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

Adult Respiratory Distress Syndrome (ARDS)
AKA: Diffuse Alveolar Damage (DAD)
Clinical: Severe respiratory deficiency, tachycardia, cyanosis, severe arterial hypoxemia
Pathophysiology: Many etiologies: shock, sepsis,
Micro: Diffuse alveolar capillary damage with hyaline membranes and type II pneumocyte regeneration

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-Schönberg 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

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)

Angiokeratoma Corporis Diffusum Universalis
AKA: Fabry's Disease

Arnold-Chiari Malformation
Mneumonic: CHASM (Cerebellum protrudes, Hydrocephalus, Spinal dysraphism, Medulla kinked)
Pathophysiology: Disproportionate growth of posterior fossa
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
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

Basal Cell Nevus Syndrome
AKA: Gorlin's Syndrome

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).

Bare Lymphocyte Syndrome
Pathophysiology: Lack of MHC Class I or both Class I & II HLA antigens resulting in varying immunodeficiency

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 Cl-
Micro: Juxtaglomerular cell hyperplasia

Basal Cell Nevus Syndrome
AKA: Gorlin's Syndrome

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

Brittle Bone Disease
AKA: Osteogenesis Imperfecta
Clinical: Bone fragility, fractures, blue sclera, bony abnormalities in middle and inner ear, abnormal teeth
Pathophysiology: Hereditary disorders of collagen synthesis, mainly type I collagen (90% of bone matrix)

Bruton's Agammaglobulinemia
Transmission: X-linked
Pathophysiology: Defective B cell maturation
Diagnosis: Near-total absence of immunoglobulins in serum

Budd Chiari Syndrome
Mneumonic: HAT (Hepatomegaly, Ascites/Abdominal pain, Thrombus)
AKA: Hepatic vein thrombosis
Clinical: ascites, portal hypertension, varices
Pathophysiology: Associated with polycythemia vera, pregnancy, postpartum, OCPs, paroxysmal nocturnal hemoglobinuria, intraabdominal CA (particularly hepatoma), infections, trauma, membranous webs.

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

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
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.

Chronic Granulomatous Disease
Clinical: Recurrent lymphadenopathy, HSM, rash, recurrent bacterial infections of lung
Transmission: 60% X linked (membrane component), 40% AR (cytoplasmic component)
Pathophysiology: Defect in genes encoding NADPH oxidase ® abnormality in H2O2 generation.
Diagnosis: ¯ Hct, ­ WBC, ­IgG
Micro: Bowel with LGV like findings

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 (30-50% chance by age 50), facial trichilemmomas, small bowel and colonic hamartomatous polyps (non-Peutz Jegher's), ± thyroid disease

Transmission: AD

Cytogenetics: Chromosome 10q

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

Cri du Chat Syndrome
Clinical: mewing cry, microcephaly, micrognathia, hepertelorism, antimongoloid palpebrae, round facies with epicanthal folds, mental retardation, physical retardation, cardiac abnormalities
Pathophysiology: del 5p-; 46 XX or 46 XY

Crigler Najjar Syndrome
Mneumonic: JUG (Jaundice, Unconjugated hyperbiliruninemia, Glucuronyltransferase)
AKA: familial non-hemolytic jaundice
Clinical: two types
I. AR: severe, kernicterus, pale yellow stool, bile bilirubin glucouronide -, not phenobarb responsive
II. AD: moderate and variable, normal stool, bile bilirubin glucouronide +, phenobarb responsive
Pathophysiology: impaired conjugation of bilirubin by the liver due to absent (Type I) or deficient (Type II) glucoronyl transferase(AKA: uridine diphosphate glucoronyltransferase or UGT) leading to an unconjugated hyperbilirubinemia
Treatment: Type II responds to phenobarbital

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

del Castillo Syndrome
Clinical: Galactorrhea following termination of birth control usage.
Pathophysiology: Pituitary shut-down of FSH and LH production.
Micro: Atrophic vaginal smear.

Dense Deposit Disease
AKA: Type II Membranoproliferative glomerulonephritis
IF: C3 in mesangial rings but not in dense deposits
EM: dense deposits in GBM

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

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

Dubin Johnson Syndrome
Mneumonic: BCP (Bilirubin, Conjugated, Pigmentation - liver)
AKA: black liver disease
Transmission: AR
Pathophysiology: absence of glucouronyl transferase leads to defects in bile canalicular transport
Diagnosis: conjugated hyperbilirubinemia
Gross: Dark-gray pigmented liver

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

Ehler's Danlos Syndrome
Clinical: Clinically and genetically heterogeneous group of disorders that result from some defect in collagen synthesis and structure. 10 clinical variants, most show cutis hyperelastica and hyperextendible joints.
EDS Type I: +diaphragmatic hernia
EDS Type IV: +rupture of colon and large arteries (rick in type III collagen)
EDS Type VI: +corneal rupture and retinal detachment
Type IV: mutation in type III collagen gene, pro a1 (III) chains, secretion defect or structurally abnormal
Type VI: mutation in lysyl hydroxylase (enzyme for cross-linking collagens I and III)
Type VII: mutation in conversion of type I procollagen to collagen
Type IX: copper metabolism defect, high in cells, low in serum & ceruloplasmin; copper-dependent enzyme lysyl oxidase essential for cross-linking collagen
Type IV: AD
Type VI: AR
Type VII: AD (dominant negative: mutant chains interfere with the formation of normal collagen helices)
Type IX: X linked recessive

Eisenmenger's Syndrome
Clinical: reversal of congenital left to right shunt (e.g. ASD, VSD, PDA), pulmonary hypertension, RVH, cyanosis

Empty Sella Syndrome
Clinical: pituitary insufficiency, panhypopituitarism
Pathophysiology: Multiple origins: herniation of sunarachnoid into sella with compression atrophy of pituitary by CSF, Sheehan's Syndrome, infarction of adenoma followed by scarring, ablation of pituitary by radiation and scarring
Micro: Ususally some residual viable tissue remains, but mostly gliotic scar.

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

Fetal Alcohol Syndrome
Mneumonic: GAMMAS (Growth retardation, Alcohol, Microcephaly, Maxillary hypoplasia, ASD, Short palpebral fissures)
Clinical: microcephaly, facial dysmorphology (short palpebral fissure, maxillary hypoplasia), malformations of the brain, cardiovascular system (strial septal defect) and genitonurinary system
Pathophysiology: acetaldehyde crosses placenta

Fetal Hydantoin Syndrome
Clinical: IUGR, mental retardation, dysmorphic facies, sleft lip, cardiac abnormalities, ambiguous genitalia

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
Transmission: AD; APC gene 5q21 variable expressivity

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
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-Barré 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
AKA: Idiopathic pulmonary fibrosis, Usual interstitial pneumonitis (UIP)

Hand-Foot-and-Mouth Disease
Clinical: pearly grey vesicles on fingers, toes, palms, soles, buccal mucosa and tongue
Pathophysiology: Coxsackie A-16

Hand-Schüller Christian Disease
AKA: Multifocal Langerhans' Cell Histiocytosis
Clinical: Triad of calvarial defects, diabetes insipidis and exopthalmos in patients with Langerhans Cell Histiocytosis (compare to Letterer-Siwe Disease).
Histiocytic infiltrates in multiple tissues and involvement of pituitary stalk in 50% leads to diabetes insipidus. Seborrhea-like skin eruption typically present.
EM: Rod shaped inclusions in Langerhans cells (Birbeck granules)
Prognosis: Relatively benign course. Lesions spontaneously regress in 50% and in 50% cured by chemoRx.

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.
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

Clinical: Hemolysis, Elevated Liver function tests, Low Platelets
Pathophysiology: Caused by severe toxemia of pregnancy

Hemolytic Uremic Syndrome
Clinical: sudden onset hematemesis/melena after GI/flu-like prodrome; severe oliguria, hematuria, microangiopathic hemolytic anemia, neurological changes in children. Familial form - more benign course. In adults associated with postpartum complications (retained placenta), OCPs.
Pathophysiology: infectious etiology include; Salmonella typhi, E. coli, Shigella, Clostridia

Henoch-Schonlein Purpura
Mneumonic: GAAACC (Glomerulonephritis, IgA, Arthralgias, Angiitis, Colic, C3)

Hereditary Angioneurotic Edema
Clinical: Episodic edema of skin, extremities, laryngeal and GI mucosa provoked by emotional stress or trauma
Transmission: AD
Pathophysiology: C1 inhibitor deficiency

Hereditary Non-Polyposis Colon Cancer Syndrome
Clinical: Early onset colon cancers at a young age <50 years, association with endometrial and ovarian cancers in some families.
Represent 2-4% of all colonic cancers
Transmission: AR; patient inherits one defective copy and the "second hit" is in colonic epithelium.
Pathophysiology: Defects in DNA repair genes hMSH2, hMLH1, hPMS1, hPMD2. When damaged, this leads to mismatch repair defects and microsatellite instability (expansions and contractions in fixed "microsatellite sequences", tandem repeats).
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.

Juvenile Polyposis Coli
Clinical: Multiple hamartomatous polyps in stomach and colon.
Transmission: AD.

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, self-mutilation
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

Löeffler'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

Mallory Weiss Syndrome
AKA: Mallory Weiss Tear
Clinical: Small tears in the esophagus as a result of prolonged vomiting.
Gross: Linear, irregular tears at GE junction or proximal gastric mucosa.

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 Sjögren'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

Milwaukee Shoulder Syndrome
Clinical: Hydroxyapetite arthropathy affecting knees and shoulders

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

Multiple Endocrine Neoplasia I (MEN I)
AKA: Wermer's Syndrome
pituitary adenoma
parathyroid adenoma > hyperplasia
pancreatic islet cell adenoma
also: thyroid and adrenal cortical neoplasms, gastric hypersecretions and peptic ulcerations
Cytogenetics: 11q11-13

Multiple Endocrine Neoplasia IIa (MEN IIa)
AKA: Sipple's Syndrome
parathyroid C cell hyperplasia or adenoma
medullary carcinoma, thyroid
pheochromocytoma (bilateral 70%)
Pathophysiology: Germ line mutation of RET proto-oncogene on chromosome 10
Cytogenetics: 10q11.2

Multiple Endocrine Neoplasia IIb (MEN IIb)
AKA: Mucosal Neuroma Syndrome
medullary carcinoma, thyroid
pheochromocytoma (often bilateral)
mucosal neuromas
Marfanoid habitus
Cytogenetics: 11q11-13

Nelson's Syndrome
Clinical: hyperpigmentation, Cranial nerve III damage (opthalmoplegia), skin pigmentation
Pathophysiology: post-adrenalectomy hyperplasia of the pituitary gland (corticotroph cells)
Diagnosis: ­ ACTH
Micro: adenomatous enlargement of the pituitary with a carcinomatous histologic picture

Neurofibromatosis I (NF I)
AKA: "Peripheral" NF, Von Recklinghausen's Disease
Clinical: 1 in 3000. Multiple neurofibromas, plexiform neurofibromas, café 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.

Neurofibromatosis II (NF II)
AKA: "central" NF, acoustic NF
Clinical: 1 in 40,000-50,000. Bilateral acoustic schwannomas, café au lait spots, (NO Lisch nodules), meningiomas, cerebellar astrocytomas, ependymomas of spinal cord, schwannosis (benign nodular ingrowth of Schwann cells into spinal cord), meningioangiomatosis, glial hamartomas.
Transmission: AD
Cytogenetics: del 22q12. Tumor suppressor gene, product called merlin similar to cytoskeletal proteins.

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.

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

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
Clinical: pain in pinky (ulnar nerve distribution), miosis, ptosis, anhidrosis,
Pathophysiology: upper lobe mass impinges on sympathetic chain or brachial plexus

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

Paroxysmal Nocturnal Hemoglobinuria
Clinical: Recurrent bouts of intravascular hemolysis leading to complement-mediated lysis of RBC, leading to a chronic hemolytic anemia
Pathophysiology: Cells lack ability to express phosphatidylinositol-linked membrane proteins, including DAF (decay accelerating factor, a complement regulator)

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

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.

Porphyria Cutanea Tarda
Clinical: vesicles on the back of the hand; association with ETOH, DM
Transmission: AD
Diagnosis: urine turns orange/red under wood's light

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.

Riley Day Syndrome
AKA: familial dysautonomia

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

Scalded Skin Syndrome
AKA: Toxic Epidermal Necrolysis (TEN)
Clinical: Rapid subepidermal blebbing and sloughing of skin with scant inflammatory changes occuring in children and occasionally adults
Pathophysiology: Staphylococcus

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. Clinically presents with gonadal deficiency, hypothyroidism or adrenocortical insufficiency.
Pathophysiology: Due to shock but may be secondary to DIC, sickle cell anemia, cavernous sinus thrombosis, temporal arteritis or trauma

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: Sjögren's syndrome occuring without another autoimmune disorder (like rheumatoid arthritis)

Sipple's Syndrome

Sjögren'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 Sjögren'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 Sjögren'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

Syndromic Large Cell Calcifying Sertoli Cell Tumor
Clinical: < 20 years old, LCCSCT, frequently bilateral; pituitary tumor; pigmented nodular adrenal hyperplasia, cardiac myxomas, Peutz Jegher's polyps

Systemic Lupus Erythematosus
Mnemonic: SOAPBRAIN M.D. (see Clinical)
15-50/100,000 8xF>M, 3x Black females>white females; 50% concordance in identical twins
6% associated with complement C2 deficiency
Serositis: pleuritis/pericarditis
Oral ulcers
Arthritis/synovitis (usually peripheral polyarthritis)
Blood Dyscrasias: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia
Renal: proteinuria, casts, hematuria, azotemia
Immune abnormalities: LE cells, anti-dsDNA, anti-Smith, VDRL/RPR+, decreased C3
Neurological Disease: seizures, psychosis in the absence of drugs or known metabolic derangements
Malar rash
Discoid rash
With pregnancy there is an increased incidence of pre-eclampsia, uterine infection, SAb, prematurity, IUGR, congenital heart bloack and endomyocardial fibrosis. There is also exacerbation of disease with decreased renal 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

Toxic Shock Syndrome
Clinical: Volume-resistant shock, diffuse macular rash, conjunctivitis, sore throat, GI upset.
Pathophysiology: Staphylococcus infection (via tampons or wounds)

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

Vanishing bile duct syndrome
Micro: irreversible loss of of bile ducts in >50% of portal tracts following liver transplantation

von Gierke Disease
AKA: Type I glycogenosis
Clinical: Hepatomegaly, renomegaly, hypoglycemia (convulsions), hyperlipidemia, hyperuricemia, gout, skin xanthomas, platelet dysfunction, hepatic adeomas
Pathophysiology: Deficiency of glucose-6-phosphatase
Prognosis: With treatment most survve and develop late complications (hepatic adenomas)

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

Von Recklinghausen's Disease
AKA: Neurofibromatosis I

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

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
Pathophysiology: Thiamine (vitamin B12) deficiency
Gross: Hemorrhagic lesions in mammillary bodies

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)