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Ann's M2M - Weeks 3, 4 > Diseases > Flashcards

Flashcards in Diseases Deck (26):


NF1, autosomal dominant
penetrance: 100% in adults; <50% in children

cafe au lait spots, neurofibromas; Lisch nodules (hamartomas) in the iris; mental retardation


Cystic Fibrosis

CFTR, autosomal recessive
1 in 2000 - 2500 white children

progressive pulmonary disease, exocrine pancratic insufficiency, obstructie azoospermia, elevated sweat chloride concentration, growth failure, meconium ileus


Turner syndrome

45, X

short stature, swelling, broad chest, webbed neck, low hairline, low-set ears
cognitive deficits: visuospatial, mathematical & memory
typically sterile, amenorrhea (non-working ovaries)


Edwards syndrome

Trisomy 18

Intrauterine growth retardation
Hypertonicity - clenched hands, narrow hips
CNS abnormalities - posterior fossa anomalities, severe intellectual disabilities, seizures
Congenital heart disease


Patau syndrome

Trisomy 13

Normal or deficient growth
CNS abnormalities - holoprosencephaly, severe intellectual disabilities
Facial clefts, polydactyly, renal dysplasia, congenital heart disease, omphalocele, dermal defects


Klinefelter syndrome

47 XXY

Tall, hypogonadism, underdeveloped secondary sexual char., gynecomastia, usually in fertile, language impairment

1/1000 live births
50% of cases = patetnal meiosis I failure of recombination in pseudoautosomal regions

15% of cases = mosaicism (46, XY / 47, XXY)


47 XYY syndrome

Indistinguishable physically / mentally from normal males

1/1000 live births
inc. risk of behavioral & educational problems; delayed speech / language


Charcot-Marie-Tooth Disease

Duplication of 17p11.2 which contains the gene for peripheral myelin protein-22 (PMP-22)

weakness of the foot and lower leg muscles
foot deformities (hammer toes)
weakness & muscle atrophy of the hands (late in the disease course)
all forms of the disease affect peripreal nerves.

*of note, due to dosage differences, deletion in the same region of chr 17p leads to a different peripheral myelin disease HNLPP (p. 97)


List the various mechanisms that lead to Down Syndrome.

1. Meiosis I nondisjunction
2. Robertsonian Translocation
3. Isochromosome
4. Mosaic Down Syndrome
5. Partial trisomy 21


Velo-Cardio-Facial syndrome


cleft palate, lateral nasal buildup, cardiac septal defects
"Contiguous Gene Syndrome"


DiGeorge syndrome


absent or hypoplastic thymus (T-cell abnormalities = a lot of infections) & parathyroids, congenital heart disease (outflow tract)


List at least 4 contiguous gene syndromes (as discussed in class)

DiGeorge syndrome
Prader-Willi syndrome
Velo-Cardio-Facial syndrome
Angleman syndrome


Chronic Myelogenous Leukemia

46, XX t(9;22)(q34;q11.2) (95% of patients)

Reciprocal Translocation between chromosomes 9 and 22.
Philadelphia chromosome: BCR gene from chrom. 22 and the ABL gene from chrom. 9 fuse. BCR-ABL fusion gene is a tyrosine kinase.


Chronic Myelogenous Leukemia

Cancer of the white blood cells
unregulated growth of myeloid cells in the bone marrow
accumulation of these cells in the blood

treated with tyrosine kinase inhibitors (imatinib, gleevec)


For DiGeorge syndrome remember CATCH-22

Cardiac abnormality
Abnormal facies
Thymic aplasia
Cleft palate
Chromosome 22 del(22q11)


Beckwith-Wiedmann syndrome

Uniparental Disomy for a portion of chr 11

large at birth, enlarged tongue, protrusion of the umbilicus
severe hypoglycemia, malignant neoplasms of kidney, adrenal and liver

see p. 79; also a focus of "ghost in your genes" video recommended by Dr. Johnson


Huntington Disease - genetics

HD allele - expansion of a polyglutamine encoding repeat (CAG) in exon 1 of the HD gene
normal allele has 10-26 CAG repeats
mutant allele has >36 CAG repeats

Age at disease onset inversely proportional to # CAG repeats in HD gene
Reduced penetrance for 36-41 CAG repeats in HD gene
80% juvenile pts inherit from father
Mean age of onset is 35-44 years
Median survival after diagnosis is 15-18 years


Huntington Disease - clinical presentation

Progressive motor, cognitive and psychiatric abnormaities
Motor: voluntary and involuntary movement disturbances; Chorea
Cognitive: language (later onset), behavioral social disinhibition, aggression, outbursts, apathy, sexual deviation, increased appetite
Psychiatric: personality changes, affective psychosis, schizophrenia


Ellis-van Creveld syndrome

Autosomal recessive
Ex. of the Founder Effect in Old Order Amish populations

short-limbed dwarfism, polydactyly, abnormal nails & teeth, heart defects


Type I Tyrosinemia

Autosomal recessive
Ex. of Founder Effect in French-Canadian region: Lac Saint Jean in Quebec

Hepatic failure, renal tubular dysfunction - deficiency in fumarylacetoacetase (enzyme in the degradation pathway of Tyrosine)
1/685 in Lac Saint Jean region of Quebec
1/100,000 in other parts of Quebec, Sweden and Norway


Osteogenesis Imperfecta genetics...

Type-1 collagen deficiency (most common)
8 types in all from different genetic mutations
Most common mutations in COL1A1 or COL1A2 autosomal dominant; 60-100% de novo mutations
(some autosomal recessive versions exist)

1/20,000 live births


Sickle Cell Anemia genetics...

SNP of Beta-globin gene Glu6Val
Beta-globin gene is located at 11q15.4

Confers Heterozygous Advantage against malaria
Common in regions with more malaria

*(E6V glutamic acid at position 6 changed to valine; GAG -> GTG; A to T mutation


HNF1-alpha mutation

Mature Onset Diabetes of the Young - 3
most common (70%) of all MODY's
HNF1-alpha is a homeobox trxn factor (important for differentiaton of beta cells)
Different mutations within the HNF1-alpha gene lead to variable expressivity of onset age
is a considered a type 2 diabetes but insulin dependence eventually develops late (after many years with disease, beta cells deteriorate)

treat with sulfonylureas


Duchene Muscular Dystrophy

X-linked recessive
Gower maneuver
giant calves
muscle wasting, extra connective tissue
progressive loss of respiratory function (diaphragm)


Becker muscular dystrophy

less severe - point (in frame mutation)

same gene location (Xp) as duchenne m.d.



autosomal dominant
chr. 4, fibroblast growth factor receptor
FGFRc - inhibits proliferation of chondrocytes
mutation leads to shortening of the long bones --> short stature
1 in 25,000