| 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 |
|
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 |
|
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. |
| 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) |
| AKA: Fabry's Disease |
|
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 |
| 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 |
|
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 |
| 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 |
| 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 |
| 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 |
| Clinical: Leukemia, GI carcinoma |
| Transmission: AR |
| Pathophysiology: spontaneous chromatid breakage |
| 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 |
|
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 |
| 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 |
| 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. |
| 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 |
| 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 |
|
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 |
|
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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Pathophysiology:
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 |
| Transmission: 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 |
| 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 |
| 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 |
| Pathophysiology: |
|
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 |
| 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 |
| 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. |
| 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 |
|
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) |
| Clinical: |
| 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
|
| AKA: HNPCC |
| 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 |
| 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 |
| 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 |
| 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 |
| 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%. |
| 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 |
| 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. |
| 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 |
| 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 |
| 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 |
| AKA: Wermer's Syndrome |
| Clinical:
pituitary adenoma parathyroid adenoma > hyperplasia pancreatic islet cell adenoma also: thyroid and adrenal cortical neoplasms, gastric hypersecretions and peptic ulcerations |
| Transmission: |
| Pathophysiology: |
| Cytogenetics: 11q11-13 |
| AKA: Sipple's Syndrome |
| Clinical:
parathyroid C cell hyperplasia or adenoma medullary carcinoma, thyroid pheochromocytoma (bilateral 70%) |
| Transmission: |
| Pathophysiology: Germ line mutation of RET proto-oncogene on chromosome 10 |
| Cytogenetics: 10q11.2 |
|
Multiple
Endocrine Neoplasia IIb (MEN IIb)
|
| AKA: Mucosal Neuroma Syndrome |
| Clinical:
medullary carcinoma, thyroid pheochromocytoma (often bilateral) mucosal neuromas Marfanoid habitus |
| Transmission: |
| Pathophysiology: |
| 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 |
| 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. |
| 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 |
| 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 |
|
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
|
| Clinical: pain in pinky (ulnar nerve distribution), miosis, ptosis, anhidrosis, |
| Pathophysiology: upper lobe mass impinges on sympathetic chain or brachial plexus |
| AKA: Oculoglandular syndrome |
| Clinical: swelling of the eye, jaw and high cervical lymph nodes caused by cat-scratch disease |
| Pathophysiology: Bartonella henselae |
| AKA: PNH |
| 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 |
| 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 |
| 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 |
| 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- |
| 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
|
| AKA: MEN IIa |
|
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) |
| AKA: SLE |
| 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) Photosensitivity Blood Dyscrasias: hemolytic anemia, leukopenia, lymphopenia, thrombocytopenia Renal: proteinuria, casts, hematuria, azotemia ANA+ 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 |
| 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) |
| 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 |
| 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 |
| 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) |
| 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 |
| 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 |
| 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) |
|
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