genetic conditions for usmle
Post on 03-Apr-2018
218 Views
Preview:
TRANSCRIPT
7/28/2019 Genetic conditions for USMLE
http://slidepdf.com/reader/full/genetic-conditions-for-usmle 1/2
Condition Basic Mechanisms Clinical Features Other Cancers
Hereditary breast-ovarian cancer syndromeAD; BRCA1 and
BRCA2
Breast cancer, ovarian cancer.
Rx: surgery/chemo, cancer
surveillance, prophylactic
sur er
BRCA1- prostate and colon; BRCA2-
laryngeal, colon, stomach, bile duct,
hematologic and melanoma
CowdenAD; PTEN gene (tumor
suppressor)
GI hemartomatous polyposis;Macrocephaly, Facial/buccal
papules
Breast cancer, thyroid cancer,
endometrial cancers
Li FraumeniAD; TP53 tumor
suppressor
soft tissue sarcoma,
osteosarcoma, bilateral breast
cancer, CNS tumors
very high cancer risk. Early onset.
leukemia, brain, adrenal cortical
cancer, melanoma, etc
Peutz-Jeghers syndrome AD, STK11 genehyperpigmented macules -
lips/mouth, GI hemartomatous
polyps
childhood GI hamartomas/cancer,
breast cancer, ovarian cancer
n o n -
p o l y p o s i s
Lynch syndrome
AD, MLH1 and MSH2
(mismatch repair,
caretaker)
NPNCC-related tumors:
colorectal, endometrial, ovarian,
urinary tract; Rx: Colectomy,
Cancer surveillance
colon, endometrium, ovary,
stomach, small intestine,
hepatobiliary tract, urinary tract,
brain, skin
CowdenAD; PTEN gene (tumor
suppressor)
hamartomatous polyps;
facial/buccal papules
Breast cancer, thyroid cancer,
endometrial cancers
Peutz-JeghersAD; TP53 tumor
suppressor
hamartomatous polyps;
hyperpigmented macules
childhood GI hamartomas/cancer,
breast cancer, ovarian cancer
familial adenomatous polyposis (FAP)
AD; APC gene tumor
suppressor
(gatekeeper)
adenomatous polyps;
attenuated FAP: fewer polyps
Rx: surgery/chemo,
cancersurveillance, prophylactic
surgery
extracolonic tumors (upper GI,
desmoid, osteoma, thyroid, brain)
gardner syndrome: + osteomas
and soft tissue tumors; turcot
syndrome: +CNS tumors
(medulloblastoma);
Fanconi's anemiaAR; chromosomal
breakage disorder
Radial hypoplasia (absent radii
and thumbs), pancytopenia Rx:
bone marrow transplant
leukemia, myelodysplasic
syndrome, solid tumors, liver
short stature,
hyper/hypopigmentation,
pancytopenia,
urogenital
abnormalities
Ataxia telangiectasia
AR; chromosome
breakage disorder
ataxia, telangiectasias, cancer
risk lymphoma, leukemia
Von Hippel-Lindau disease
AD; VHL gene tumor
suppressor
(gatekeeper)
Hemangioblastoma (cerebellum,
retina, spinal cord),
pheochromocytoma (HTN),
renal cell ca
MEN 1
AD; MEN1 gene tumor
suppressor
PPP (pituitary, parathyroid,
pancreas)
MEN 2
AD; RET gene, proto-
oncogene
thyroid-medullary cancer,
pheochromocytoma,
marfanoid habitus mucosal neuromas
O t h e r
Retinoblastoma
AD; RB1 tumor
suppressor
retinoblatoma (bilateral =
hereditable, unilateral =
nonheritable)
heritable: extraocular
osteosarcomas, sarcomas,
melanomas
B r e a s t a n d o v a r i a n c a n c e r
s y n d r o m e s
m a n y p o l y p s
C o l o n C a n c e r
a u t o s o m a l r e c e s s i v e
E n d o c r i n e
7/28/2019 Genetic conditions for USMLE
http://slidepdf.com/reader/full/genetic-conditions-for-usmle 2/2
Condition Basic Mechanisms Clinical Features Other Dx DDx
Galactosemia
AR; Galactose-1-phosphate
uridyltransferase (GALT)
enzyme
cataract, hepatomegaly, E. coli
sepsis. Rx: dietary intervention,
lactose restriction
galactosuria, FTT,
vomiting/diarrhea,
hepatomegaly, e coli sepsis
Maple Syrup UrineDisease
AR; branched-chain alpha-
ketoacid dehydrogenaseenzyme complex (BCKAD);
aminoacidopathy
lethargy - coma, seizures, maple
syrup odor; Rx: dietary
intervention, BCAA restriction
poor feeding, maple syrupodor
elevated BCAAs, enzymeanalysis
ketosis, no acidosis,no hyperammonemia
Methylmalonic
acidemiaAR; organic acidemia
severe ketoacidosis, seizures,
encephalopathy
severe ketoacidosis,
hyperammonemia,
neutro enia, vomitin
ketosis, acidosis,
hyperammonemia
Ornithine
Transcarbamyl-ase
deficiency (OTC)
X-linked recessive; urea
cycle disorder
Coma, seizures,
hyperammonemia; Rx:
hemodialysis
hyperammonemia, respiratory
alkalosis, protein avoidance,
FTT, vomiting
expressed in females due
to lyonization
hyperammonemia,
no ketosis, no
acidosis
PKU
AR, phenylalanine
hydroxylase enzyme,
aminoacidopathy
MR, blue eyes/fair skin,
eczematous rash. Rx: dietary
phenylalanine restriction
musty body odor,
hyperactivity, seizures
newborn screen, plasma
phenylalanine
homocystinuriaAR, cystathionine beta
synthase enzyme (CBS)
ectopic lentis,
thromboembolism, MR/DD,
marfanoid. Rx: dietary protein
restriction
newborn screen; urine
homocystine, plasma Aas,
enzyme analysis, DNA
anal sis
Amino Acidopathy Organic Acidemia Urea Cycle disorder
PKU methylmalonic acidemia OTC deficiency
MSUD
homocystinuria
Condition Basic Mechanisms Clinical Features Other Dx DDx
Leber Hereditary
Optic Neuropathy
(LHON)
mtDNA point mutations bilateral vision loss- young adultbilndness, neuropathy,
myopathy
opthalmology exam,
mtDNA analysis
MELAS
mtDNA pt mutation:
m3243A>G MT-TL1 gene
(tRNA)
mitochondrial
encephalomyopathy, lactic
acidosis, stroke-like episodes
cardiomyopathy, arrhythmia,encephalomyopathy, stroke
like episodes, seizures,
hearing loss, lactic acidosis,
vomiting
lactate, brain imaging,
muscle biopsy, mtDNA
analysis
p e r o x i s o m
a l
Zellweger syndrome
AR; peroxisomal disease
(no peroxisomes are
formed)
hypotonia, facial dysmorphism,
elevated VLCFA
Facial dysmorphism: high
forehead, large fontanels,
hypotonia, seizures, poor
feeding liver dysfunction
biochem testing including
VLCFA levels, DNA
analysis
F a t
t y - a c i d o x i d a t i o n
d e f e c t Medium-Chain Acyl-
Coenzyme A (MCAD)
deficiency
AR; MCAD enzyme, fatty
acid oxidation defect
hypoketotic hypoglycemia,
myopathy, cardiomyopathy. Rx:
avoid fasting, frequent feedings,
carbs
normal at birthy, vomiting,
sudden infant death
newborn screen, plasma
acylcarnitines, enzyme
and/or DNA analysis
Condition Basic Mechanisms Clinical Features Other Dx DDx
G l y c o g e n
von Gierke's disease
(GSD I)
AR; glucose 6-phosphatase;
glycogen storage disease
hypoglycemia, massive
hepatomegaly, lactic acidosis; Rx:
avoid fasting, frequent feedings,
carbs
growth failure, hypoglycemic
seizures
clinical features, liver
enzyme analysis
and/orDNA analysis
G
l y c o g e +
l y
s o s o m e
Pompe disease
AR; acid alpha glucosidase
(GAA) enzyme; glycogen
storage and lysosome
storage
cardiomegaly/HCM, macroglossia,
muscle weakness. Rx: Enzyme
replacement therapy
cardiomegaly, macroglossia,
hypotonia, poor feeding,
failure to thrive, elevated
creatinine kinase
blood enzyme activity
and/or DNA analysis
von gierke's
symptomes +
cardiomegaly
Fabry
X-linked; alpha
galactosidase enzyme,
lysosomal storage disease
corneal opacities,
angiokeratomas,
acroparesthesias. Rx: enzyme
replacement therapy
cardiomyopathy, transient
ischemic attacks, stroke,
neuropathy, angiokeratoma,
proteinuria, kidney failure,
irritable bowel s ndrome
clinical features. Male:
enzyme analysis and/or
DNA analysis. Females:
DNA analysis
Gaucher
AR; glucosylceramidase
enzyme, lysosomal storage
disease
anemia, hepatosplenomegaly, no
cherry red spot
absence of primary CNS
disease, bone disease/pain,
lipid-laden macrophages with
wrinkled paper inclusions
clinical features, enzyme
analysis and/or DNA
analysis
no cherry red spot
Tay Sachs
AR; hexoasminidase A
enzyme; lysosomal storage
disease
infant, cherry red spot,
progressive neurodegeneration
hypotonia, loss of motor skills,
hyperacusis neurodeneration:
seizures, spasticity; normal
sized liver and spleen
clinical features, enzyme
analysis and/or DNA
analysis
cherry red spot
Hurler syndrome,
Mucopolysaccharidos
es type I (MPS I)
AR, [all MPS =AR except
Hunter (MPS II) is X-linked];
lysosomal storage disease.
coarse features, MR,
hepatosplenomegaly. Rx: ERT,
bone marrow transplant
macrocep a y, cornea
opacities, enlarged tongue,
valvular heart disease,
hearing loss, joint stiffness,
dwarfism, Urine: dermatan
blood enzyme activity
and/or DNA analysis
i n t o x i c a t i o n p h e n
o t y p e s
n o n i n t o x i c a t i o n
p h e n o t y p e s
INTOXICATION
General characteristics of intoxication pathways: normal delivery, symptom-free before crash. Poor feeds, weak suck, weight loss, vomit, weak cry,
hypertonia/hypotonia/seizures/coma
ENERGY DEFICIENCY
L y s o s o m e
prenatal abnormalities (absent corpus callosum), no symptom-free interval, flaccid birth, poor respiratory effort, several hypotonia, dysmorphology, usually craniofacial, true
seizures from birth
m i t o c h o n
d r i a l
STORAGE DISEASE
Glycogen storage: metabolic symptoms - hypoglycemia, hepatomegaly and no splenomegaly
Lysosome storage: hepatosplenomegaly, CNS, bone, skin. Symptoms are progressive
top related