Aneuploidies (somatic and sex) Flashcards by Aubrey Hite

What are the three aneuploidies common with postnatal survival?

Trisomy 21, 18, 13

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What is the prevalence of Down syndrome?

1:660-1:700

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What are some of the general features of T21?

hypotonia, hyperflexiblty of joints, small stature, learning disability

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What hand/feet malformations are seen in T21?

clinodactlyly, single transverse palmar crease, gap btwn 1st and 2nd toe, crease btwn 1st and 2nd toe

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What are common cardiac malformations in T21?

atrioventricular setpal defect
patent ductus ateriosis
ventricular septal defect

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What are common GI tract features in T21?

duodenal atresia (double-bubble)
anal atresaia
agangliosis of colon
reflux

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What are common MSK features of T21?

11 pairs of ribs vs. 12

predisposition to hip dislocation

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What are the cytogenetic findings with T21?

95% result from nondisjunction
3-4% result from Robertsonian translocation (usually 21q w/ an acrocentric chromosome -> 14 or 22) - no relation w/ maternal age
1-2% mosaicism

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Prenatal issues seen in T21?

at least 20% are SB

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Infant features of T21?

hypotonia
poor moro relfex
increased flexiblty of joints
excess nucahl skin
flat facial profile
upslanting eyes
small ears
clinodactylly 
transverse palmar crease
congenital heart defect (roughly 50%)

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Features seen in children with T21? Guidance?

hearing loss -> hearing screens, tubes may help prevent infection and improve hearing
delayed tooth eruption and growth
celiac disease (7-16%)
hypo- and maybe hyperthyroidism

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Eye features in children w/ T21?

should see an ophthalmologist
cataracts (congenital or acquired)
thinning and stretching of cornea is common

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Individuals with Down syndrome have an increased lifetime risk of this cancer:

Leukemia

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Features seen in adults with Down syndrome?

early-onset Alzheimer’s disease (in their 40s)
incontinence
hearing loss
infertility in males

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Trisomy 18 is also known as:

Edward syndrome

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What is the incidence of trisomy 18?

1:6000-1:8000 birth

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How do we note the karyotype of an individual with Edward syndrome?

47,XX,+18

47,XY,+18

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Which sex seems to survive to term more in pregnancies affected by trisomy 18?

Females (3:1)

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What are the features seen in T18?

prominent back of the skull
unusual ears
small mouth and jaw
clenched hands 
flexed big toes w/ prominent heels

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What general characteristics do we see in pregnancies with t18?

poor fetal movement
1/3 premature
1/3 past due date
polyhydramnios
single umbilical artery
hypertonicity postnatally
abdominal hernia
males w/ undescended testes

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What are the survival stats for infants born with trisomy 18?

50% mortality within the 1st wk

most don’t live past a year

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What syndrome is also known as trisomy 13?

Patau syndrome

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What is the incidence of trisomy 13?

1:12,000 live birth

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What features are seen in more than 50% of trisomy 13?

Cleft lip and palate
small for gestational age
postaxial polydactyly
clenched hands (outer finger overlapping middle)
CNS issues
Holoprosencephaly (severe -> cyclopia)
microcephaly
sloping forehead
congenital heart defect
renal issues
undescended testes or hypoplastic ovaries
rocker bottom feet
cutis aplasia

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What are some other features seen in trisomy 13?

hydrocephalus spina bifida omphalocele kidney abnormalities

Inactivated Xs replicate _______ than active ones.

slower

What parts of the X chromosome lead to their inactivation?

CpG islands are highly methylated regions -> inactivation

What percentage of genes on the X chromosome escape inactivation? On which arm are most of them located?

10-15% | more on Xp than Xq

Xp is associated with what physical feature? Xp and Xq?

stature | ovarian function

Where is the X inactivatin center located? | What gene is associated with this?

Xq13 | XIST

What is the product and function of XIST?

noncoding RNA | stays closely associated w/ inactive X (only expressed from inactive X)

X inactivation is random unless?

there is an abnormal X chromosome | there is an x;autosome translocation

Which X is inactivated if there is an abnormal X?

the abnormal X is preferentially inactivated | ex: Xi (isochromosome)

Which X is inactivated when there is an x; autosome translocation?

If translocation is unbalanced -> abnormal X is inactivated | if translocation is balanced -> normal X is inactivated

What syndrome is written as 45,X?

Turner syndrome

What is the incidence of Turner syndrome?

1:4000 live births

what are the major features of Turner syndrome?

``` low posterior hairline (looks like short neck) swelling of hands and feet broad chest and wideset nipples short stature ovaries not developed unusual shape and rotation of ears narrow maxilla or palate micrognathia ```

What cardiac abnormalities are seen in individuals with Turner syndrome? Which is emergent? What procedure should they have to assess?

``` bicuspid aortic valve coarctation of the aorta (urgent) aortic valve stenosis hypoplastic left heart mitral valve prolapse ``` echocardiogram

What are the cytogenetics seen with Turner syndrome?

``` 50% 45,X 15% 46,X,i(Xq) 15% 45,X/46,XX mosaic 5% 45,X/46,X,i(Xq) mosaic 10% other abnormal karyotypes ``` ring X chromosome Long arm deletion short arm deletion

What gene is associated with short stature? Where is it located?

SHOX Xp22.3 Yp11.3 located in pseudoautosomal region - errors in recombination can interfere

What cognitive features are seen in Turner syndrome?

intelligence at or above the average deficient in spatial perception, perceptual-motor organization, and fine motor execution nonverbal IQ is lower than verbal IQ

How is Turner syndrome treated?

``` growth hormone estrogen therapy (12-14yrs) ```

What adult issues are seen in individuals with Turner syndrome?

``` osteoporosis bone fractures insulin resistance (diabetes) hypertension obesity hyperlipidemia hearing loss ```

Turner syndrome prenatal outcomes? INdications?

seen in 1-2% of conceptus 99% result in spontaneous abortion single X is usually of maternal origin ``` nuchal thickening (up to cystic hygroma) swelling/fluid growth delay ```

What karyotype do we see in Klinefelter syndrome?

47,XXY

What's the incidence of Klinefelter syndrome?

1:1000 male births

What are the physical features of Klinefelter syndrome?

tall small testes and penis delayed puberty breast development

What behavioral issues are common in Klinefelter syndrome?

``` learning problems below average verbal comprehension and ability shyness and unassertiveness apparent immaturity passivity ```

What are the cytogenetics seen in Klinefelter syndrome?

50% of errors in paternal meiosis (failure of normal Xp/Yp recombination) maternal issues: most meiosis I, others in II, or postzygotic errors -> mosaicism (increase with age) 15% of individuals are mosaic more Xs, more severe cognitive deficits

How can we treat Klinefelter syndrome?

hormone treatment | refer to endocrinolgoy

What are some other trisomies and their features?

47, XXX 1:1000 taller, usually fertile, 70% have learning problems, offspring have increased risk of chromosome abnormality 47,XYY tall, increased educational and behavioral problems, normal IQ, fertility usually normal

What gene is associated with male differentiation? Where is it located?

SRY near pseudoautosomal region briefly expressed early in development to cause differentiation of testes

When do the gonads begin to differentiate? What happens if there's no SRY or it's ineffective?

around wk 6 of development | ovaries develop

What karyotypes are common in DSDs?

46,XX male | 46,XY female

What often causes infertility in men? What gene(s) are associated? Should men be referred for genetic testing? If so, what?

Azoospermia AZF gene clusters yes, if it is idiopathic -> karyotype and Y chromosome-specific testing

What is uniparental disomy?

form of nondisjunction where both chromosomes are inherited from same parent

What is isodisomy?

same sister chromosomes

what is heterodisomy?

same homolgoues inherited frome same parent

What is the typical cause of UPD?

trisomy rescue -> cell's attempt to return to disomic state in trisomic conceptus results from 2nd nondisjunction event in early, postzygotic mitotic division

22q11.2 deletion is typically detected by

CMA (microarray)

What two conditions are common genomic imprinting disorders?

Prader-Willi | Angelman

What genes are associated with male development?

SRY | TDF

Infertility in men can be associated with what changes? Where are these found?

AZF gene cluster AZFa, AZFb, AZFc Yq

Aneuploidies (somatic and sex) Flashcards

(63 cards)