increased incidence of osteosarcomas, breast cancers, adrenocortical tumors, leukemias (AD, significantly inc risk of malignancy as children or young adults)

increased incidence of (ABC):

Adrenocortical 

Breast

Brain

Blood (leukemia)

Bone (osteosarcoma)

Cancer

failure of GnRH-secreting neurons to migrate from  olfactory placode to hypothalamus leads to diminished synthesis of gonadotropic hormones by ant. pituitary

charac by: 

* primary amenorrhea

* absent 2dary sex charac

* olfactory sensory defect (anosmia)

an autosomal recessive condition that results from defects in genes that modulate DNA stability.

charac by: 

aplastic anemia and AML

principal clinical findings:

* gradual onset of marrow failure in first 5 yrs of life

* anemia

* weakness

* fatigue

* dyspnea on exertion

* thrombocytopenia c epistaxis or purpura

bilateral renal agenesis -> oligohydramnios -> limb deformities, facial deformities, pulmonary hypoplasia

caused by malformation of ureteric bud 

defect in proximal tubule transport of AA, glucose, phosphate, uric acid, protein, and electrolytes

assoc c rickets, osteomalacia, hypokalemia, metabolic acidosis, or by use of degraded/expired tetracyclines 

faulty collagen synthesis causing:

1. hyperextensible skin

2. tendency to bleed (easy buising)

3. hypermobile joints

10 types (collagen type III most freq affected -> blood vessel instability)

inheritance varies

assoc c berry aneurysms 

primary hyperaldosteronism

caused by aldosterone-secreting tumor

HTN, hypoK+, metabolic alkalosis, low plasma renin

tx: spirinolactone 

postpartum hypopituitarism

caused by infarction of pituitary gland after severe bleeding and hypoperfusion during delivery

fatigue, anorexia, poor lactation, loss of pubic and axillary hair

risk factors:
* multiple gestation
* abnormalities of placenta
* peripartum hemorrhage

aka hereditary hemorrhagic telangectasia

rare congenital vascular disorder (sporadic) (AD)

sx: port-wine stain (facial angioma), leptomeningeal angioma

clinical findings:

* mental retardation 

* seizures

* hemiplegia

* skull radiopathies (show "tram-track" calcifications) 

from pressure on hypothalamus (such as in craniopharyngioma or pituitary adenoma)

from damage of inferior parietal lobule of dominant hemisphere (such as in middle cerebral artery thrombosis or damage of contralateral angular gyrus)

results in:

from bilateral lesion of ant temporal lobes (incl amygdala)

results in:

from thiamine deficiency (esp in alcoholism)

irreversible damage; lesions found in mamillary bodies and MD nuclei of thalamus

characterized by:

due to mass effect (pressurized)

acute symmetric ascending inflammatory neuropathy with hx of resp or GI illness 1-3 wks prior to sx onset

lesion of descending hypothalamic fibers (sympathetic) in cervical chain - above T1- such as in Brown-Sequard syndrome, Pancoast tumor (squamous cell carcinoma in the superior sulcus of the lung), and late-stage syringomyelia

ipsilateral:

hemisection of spinal cord

all following losses below lesion: 

losses at level of lesion: 

If lesion occurs above T1: add Horner's syndrome 

due to lesion of S2-S4

characterized by:

lysosomal storage disease

deficient alpha-L-iduronidase  leads to accumulation of dermatan & heparan sulfate

sx: mental retardation, coarse facial features, corneal clouding, coronary artery

X-linked recessive form of Hurler's syndrome

milder phenotype

 (see Hurler's syndrome card) 

defect in cytoskeletal glycoprotein leading to combined partial B- and T-cell deficiency

X-linked

characterized by:

motor/vocal tics (unvoluntary and uncontrolled)

commonly assoc c OCD and ADHD

tx: antipsychotic agents 

caused by loss of ant spinal artery blood supply

charac by:

medial pontine syndrome

loss of paramedian branches of basilar artery blood supply

charac by:

lateral pontine syndrome

loss of AICA blood supply

charac by:

Parinaud syndrome

aka dorsal midbrain syndrome

caused by tumor in pineal region

Weber syndrome

aka medial midbrain syndrome

caused by loss of branches of PCA blood supply

chr 3 mutation (AD)

results from co-administration of SSRI with TCA, MAOIs, meperidine or dextromethorphan (may cause death)

characterized by:

charac by:

paraneoplastic syndrome assoc c small cell carcinoma of lung (ectopic ADH)

tx: demeclocycline 

conus medullaris tumor leads to compression causing the syndrome

charac by:

complication of meningococcemia

caused by bilateral hemorrhage into adrenal gland causing adrenal insufficiency

charac by:

complication of leptospirosis (10%)

charac by

22q11 defect: failure of formation of 3rd and 4th pharyngeal pouches -> thymic aplasia

charac by:

terminal or interstitial deletion of 5p

charac by:

immotile cilia due to defect in axonemal proteins (i.e. dynein arms); AR

charac by:

defect in microtubule polymerization in leukocytes, leading to dec phagocytosis

charac by:

X-linked defect affecting methylation and expression of FMR1 gene

(triplet repeat CGG may show genetic anticipation - germline expansion in female)

charac by:

* macro-orchidism

* long face c large jaw

* large everted ears

* autism 

familial form of enchondromatosis

enchondromas and hemangiomas of skin (visceral hemangiomas)

inc risk of malignant transformation into chondrosarcoma 

association of

* polyostotic fibrous dysplasia

* cafe-au-lait spots

* sexual precocity in women 

classic triad:

1. xerophthalmia (dry eyes, conjunctivitis)

2. xerostomia (dry mouth, dysphagia)

3. arthritis (rheumatoid)

also see parotid enlargement

inc risk of B-cell lymphomas

assoc c SS-A (Ro) & SS-B (La) autoAbs

mostly W 40-60 yrs old 

variant of Sjogren's (but no RA)

charac by:

* dry eyes

* dry mouth

* nasal and vaginal dryness

*chronic bronchitis

* reflux esophagitis 

HGPRT deficiency; X-linked recessive

mental retardation (mild)

spastic cerebral palsy

self-mutilation

hyperuricemia

45, XO (female)

* short stature, webbed neck, shield chest

* primary amenorrhea, infertility

* coarctation of aorta & pulmonary stenosis

* cystic hygromas - cavernous lymphangioma consisting of network of endoth-lined lymph spaces beneath epidermis 

* incidence 1/6000 female births 

47, XXY (male, but looks female)

* eunuchoid body with lack of male secondary sex charac

* hypogonadism, testicular atrophy

* dec testosterone & inhibin

* inc LH & FSH 

* incidence: 1/2000 male births

male

* excessively tall with severe acne

* no other phenotypic abnormalities

* inc risk of behavioral problems (due to very aggressive nature)

* incidence 1/1000 male births 

seroneg spondyloarthropathy 

triad of arthritis, uveitis, & conjunctivitis

HLA-B27 neg

frequently post-GI(enteritis) or chlamydia infections 

granulomatous vasculitis c eosinophilia

involves lung, heart, skin, kidneys, nerves

hallmark signs: asthma, eosinophilia, and systemic vasculitis

other features:

* heart disease (CHF)
* skin lesions (incl purpura and cutaneous and SQ nodules)

* often seen in atopic pts

* +ANCA

tx: cyclophosphamide 

occurs within first year of life of sickle cell disease patients

small infarctions in bones of hand, wrists, feet, ankles -> swelling, tenderness, warmth

Note: in adults with SCD - pain crises, acute chest syndromes, leg ulceration, priaprism, autosplenectomy, stroke 

LEMS (d/o of NM junction)

mech: IgG autoAb against voltage-dependent calcium channels at NM synapse -> inhibits ACh release -> muscle weakness

usually a paraneoplastic syndrome (often with small cell lung carcinoma)

charac by:

* gait alteration

* difficulty in rising from chair and climbing stairs

* ptosis

Note: power steadily increases with sustained contraction unlike actual Myasthenia Gravis

congenital agenesis of sacrum and/or lumbar spine leading to:

* flaccid paralysis of leg

* dorsiflexed contractures of feet

* urinary incontinence

syndrome linked very rarely to uncontrolled DM during pregnancy 

aka MEN type I  (multiple endocrine neoplasia)

* pancreas tumor (Zollinger-Ellison syndrome, insulinomas, VIPomas)

* parathyroid tumor

* pituitary tumor (prolactinoma)

presents with kidney stones and stomach ulcers 

aka MEN type II (multiple endocrine neoplasia)

AD, assoc c ret gene mutation

* medullary carcinoma of thyroid

* pheochromocytoma

* parathyroid tumor

AD inheritance 

 AD; assoc c ret gene mutation

* medullary carcinoma of thyroid

* pheochromocytoma

* oral and intestinal ganglioneuromatosis (mucosal neuromas) 

congenital hypothyroidism

major effects on skeletal & CNS development (once apparent, irreversible)  - need to screen newborns

 charac by:

* protuberant abdomen

* wide-set eyes

* dry rough skin

* broad nose

* delayed epiphyseal closure 

caused by carcinoid tumor (neuroendocrine cells)

(esp metastatic small bowel tumors secreting high levels of 5HT)

results in: (only after metastatis past liver)

* recurrent diarrhea

* cutaneous flushing

* asthmatic wheezing

* right-sided valvular disease

* inc 4HIAA in urine

rules of 1/3

* 1/3 metastasize

* 1/3 present c 2nd malignancy

* 1/3 multiple

gastrin-secreting tumor of pancreas or duodenum

causes recurrent ulcers

may be assoc with MEN type I 

uncorrected VSD, ASD, or PDA leads to progressive pulmonary HTN -> inc pulmonary resistance -> RVH -> shunt reverses from [L to R] to [R to L]

result: late cyanosis (clubbing and polycythemia) 

accessory conduction pathway from atria to ventricle (via bundle of Kent), passing AV node

consequence: ventricles begin to partially depolarize earlier -> characteristic delta wave on ECG

may result in reentry current -> SVT (supraventricular tachycardia)

classic triad:

1. decreased PR interval

2. widened QRS  interval

3. delta wave 

from consumption of large amounts alcohol during pregnancy (dose-dependent teratogen);

-cannot be diagnosed prenatally 

features:

Behavior disturbances
Brain defects
Cardiac defects
Spinal defects
Craniofacial anomalies such as:
  *Absent or hypoplastic philtrum
  *Broad upper lip
  *Flattened nasal bridge
  *Hypoplastic upper lip vermilion
  *Micrognathia
  *Microphthalmia
  *Short nose
  *Short palpebral tissue

trisomy 21

20% have congenital cardiovascular dx (most common ASD, but can also see VSD)

mutation of fibrillin gene on chr 15 (AD)

charac by:

MI complication (polyserositis)

autoimmune phenomenon resulting in fibrinous pericarditis (occurs several wks post-MI)

type of endomyocardial dx -> restrictive obliterative cardiomyopathies

endomyocardial fibrosis c intense eosinophilia and thromboembolic phenomena

mostly M
related to parasitic infections, leukemia, and immunologic reactions
 

describes both Raynaud disease (sx >3 yrs s evidence of underlying dx) and phenomenon

* Episodic bilateral digital pallor, cyanosis, and rubor
* Precipitated by cold or emotional stress; relieved by warmth

Raynaud phenomenon assoc c:

– Autoimmune diseases

– Myeloproliferative disorders

– Multiple myeloma

– Cryoglobulinemia

– Myxedema

– Macroglobulinemia

– Arterial occlusive disease

an acquired coagulopathy presenting as migratory thrombophlebitis often in a setting of underlying malignancy*

complications: pulmonary embolism, stroke, limb necrosis, and organ ischemia

*most common malignancy: lung carcinoma

less common: pancreatic cancer -> pulmonary embolism 

caused by chronic iron deficiency

charac by:

* esophageal web (dysphagia for solids, not liquids)

* achlorhydia

* glossitis

* spoon nails (koilonychia)

labs:

* dec MCV, serum Fe, iron saturation %, ferritin

* inc TIBC, RDW

clinical finding in adults with sickle cell diseas

charac by:

* vaso-occlusion of pulmonary capillaries

* chest pain, lung infiltrates, hypoxemia

* most common cause of death in these adults 

X-linked molecular defect: deficiency of CD40L on activated T-cells

charac by:

* high serum titers of IgM without other isotypes

* normal B,T-cells

* inc susceptibility to extracellular bacteria and opportunists

subtype of severe combined immunodeficiency (SCID)

-->MHC class II deficiency

charac by

* T-cells presents & responsive to nonspecific mitogens

* no GVHD

* deficient in CD4+ Tcells

* hypogammaglobulinemia 

T-cell lymphoma

involve neoplastic peripheral CD4 Th-cells

40-60 y.o.

mycosis fungoides with a leukemic phase

circulating cells are sezary cells

[image]

aka internuclear ophthalmoplegia

damage (demyelination) to MLF (unilateral) between abducent and oculomotor nuclei

causes medial rectus palsy on

* attempted lateral conjugate gaze

* monocular horizontal nystagmus in abducting eye

BUT convergence is normal

commonly seen in multiple sclerosis 

an acute febrile condition marked by severe depression of the granulocyte-producing bone marrow and by prostration, chills, swollen neck, and sore throat sometimes with local ulceration

assoc c:

* clozapine

* colchicine

* methimazole

* phenylbutazone

* propylthiouracil 

charac by

* microangiopathic hemolytic anemia

* thrombocytopenia

* renal insufficiency

can occur after infection by Ecoli O157:H7 (from undercooked beef, unpasteurized milk, unwashed hands)

compared c DIC: 

* usually does not bleed

* only platelets activated

* nl PT & PTT, nl fibrinogen

benign AR disorder

charac by:

* conjugated hyperbilirubinemia in childhood or during adult life

 * mutations in protein involved in the secretion of conjugated bilirubin into bile

* black pigment in liver

benign hyperbilirubinemia caused by mutations in the gene encoding bilirubin-UGT

* more common in males

* ~30% of the enzyme activity preserved -> benign

rare AR disorder leading to hyperbilirubinemia

charac by:

* severe congenital jaundice (serum bilirubin usually exceeds 20 mg/dL)

* complete loss of bilirubin-UGT activity in hepatic tissues -> fatal within the first 15 months of life

rare AR disorder leading to hyperbilirubinemia (do not exceed 20 mg/dL)

charac by: 

* mutations in the gene encoding bilirubin-UGT

BUT

* some activity retained -> more benign course than type I

tx: large doses of phenobarbital

in newborns:

* prematurity, maternal DM, C-section -> decreased surfactant ->widespread atelectasis -> massive intrapulmonary shunting

* complications: blindness, bronchopulmonary dysplasia 

acute alveolar-capillary damage -> noncardiogenic pulmonary edema

Risk factors:

* gram-neg sepsis

* gastric aspiration

* severe trauma c shock

* diffuse pulmonary infections, heroin, smoke inhalation

PMNs-mediated damage of alveolar capillar walls and epi cells -> leaking of protein-rich exudate -> hyaline membrane generation

clinical findings:

* dyspnea c severe hypoxemia not responsive to O2 therapy

* acute resp acidosis

complications:

* progressive interstitial fibrosis