Repro Part 3

Front 1

most structural birth defects are determined during:

Back 1

weeks 3-8

Front 2

malformation =

Back 2

inborn/congenital error of morphogenesis

Front 3

best examples of malformations:

(3)

Back 3

1. cleft lip/palate

2. neural tube defects

3, polydactyly

Front 4

70% of NTD's can be prevented with:

Back 4

folic acid throughout child-bearing years

Front 5

deformations are the result of:

Back 5

mechanical forces

e.g. club foot, bowed legs

Front 6

deformation is most common in the:

Back 6

third trimester

Front 7

disruption =

Back 7

extrinsic breakdown of, or an interference with, an **originally nl** developmental process

Front 8

best example of disruption =

Back 8

amniotic bands

Front 9

dysplasia =

Back 9

**an abnl organization of cells** into tissues and its morphologic results

- m.c.ly skeletal dysplasias, ectodernal dyslpasias

Front 10

skeletal dysplasias often have associated:

Back 10

malformations,

deformations

Front 11

tissues derived from ectoderm:

(5)

Back 11

1. skin

2. hair

3. teeth

4. nails

5. hearing

Front 12

malformation ~~

deformation ~~

disruption ~~

dysplasia ~~

Back 12

congenital;

mechanical forces;

interference of nl development

abnl tissue

Front 13

examples of minor anomalies:

(7)

Back 13

1. head shape

2. ear size/morphology

3. eyes
(spacing, telecanthus)

4. hair patterning
(widow's peak, low posterior hairline, cowlik/frontal upsweep)

5. palmar creases

6. finger/palm dermal ridge patterns

7. ridges on finger pads

Front 14

many syndromes are recognized by:

Back 14

their constellation of minor anomalies

Front 15

some minor anomalies run in families in AD fashion;

but the presence of 3 or more suggests:

Back 15

an underlying, more widespread defect in morphogenesis 

(e.g,. a syndrome of chromosomal or single gene cause)

Front 16

telecanthus =

Back 16

loss of M white sclera

Front 17

features of Waardenburg type 1:

Back 17

1. telecanthus

2. white forelock

Front 18

posterior pits on the back of the ear suggest:

Back 18

fetal overgrowth

(big babies, twins)

Front 19

difference between sequence and syndrome:

Back 19

sequence = SINGLE, PRIMARY defect with secondary or tertiary anomalies

i.e. cascade of problems derived from a single known cause

syndrome = MULTIPLE primary anomalies running together

- more than one tissue, organ system, developmental field, or region of the body is dysmorphic, dysplastic, dysfunctional, or dystrophic

Front 20

example of a sequence:

(3)

Back 20

1. NTD

2. hydrocephalus

3. talipes (club foot)

Front 21

3 causes of syndromic malformations:

Back 21

1. chromosomal abnormalities (genomic mutations)

2. single gene mutations (Mendelian disorders)

3. teratogens

Front 22

classic FAS facies =

(2)

Back 22

1. small eyes

2. smooth philtrum

Front 23

the “classic FAS face” only occurs with an exposure during:

Back 23

early gastrulation,

~ day 17 in humans

Exposures at other times clearly affect the development of the CNS and other organ systems, but do not cause the FAS facies

- looking for FAS by looking for facies will miss the point

Front 24

Fetal Alcohol Spectrum Disorders (FASD) include:

(3)

Back 24

1. FAS

2. ARND (alcohol-related neurodevelopmental disorders)

3. ARBD (alcohol-related birth defects)

Front 25

other systems affected by FAS:

(4)

Back 25

1. CV CNS: structural and functional

2. Poor linear growth, wt gain

3. Kidney

4. many others

Front 26

"nonsyndromic" malformations =

Back 26

isolated malformations

i.e. only ONE primary malformation

- all others are coincidental

Front 27

best examples of nonsyndromic malformations:

(4)

Back 27

1. ID

2. autism

3. HTN

4. Alz

Front 28

"multifactorial" ~~

Back 28

genetic predisposition interacts with environment to move a person past the threshold and into "affected" state

Front 29

“Complex” =

Back 29

combination of both single gene and multifactorial causation

Front 30

Intellectual disability ~~ not only to low IQ but also to:

Back 30

dec. in adaptive skills

- daily living, communication, social

Front 31

most causes of ID are:

Back 31

unknown

- after that, chromosomal

Front 32

any child with ID without a clear-cut diagnosis should have:

Back 32

chromosome analysis and/or chromosome microarray

Front 33

main difference b/w karyotype and microarray:

Back 33

microarray looks much closer, can pick out much smaller deletions or duplications

(gain or loss)

Front 34

neuroimaging for FX syndrome:

Back 34

MRI

- avoid CT if possible

Front 35

features of Williams syndrome:

(8)

Back 35

1. very friendly

2. great musical ability

3. delayed milestones

4. mild ID

5. hypercalcemia

6. heart issues

7. puffiness around eyes

8. big lips

Front 36

2 genes associated with deletion of 7q11.23 in Williams syndrome:

Back 36

1. ELN (elastin)

2. LIM-kinase 1

Front 37

most cases of Williams syndrome are:

Back 37

de novo deletions

Front 38

testing for Williams in other family members:

(2)

Back 38

1. offer chrome. testing with FISH to parents

2. if nl, low recurrence risk; other family members not at risk

Front 39

cleft L/P is most commonly:

Back 39

non-syndromic (~70%)

- vs. syndromic

Front 40

features of non-syndromic cleft L/P, wrt pt:

(3)

Back 40

pt has

1. no other anomalies

2. no recognized maternal/environmental exposures

3. multifactorial inheritance

Front 41

teratogens that may contribute to cleft LP:

(4)

Back 41

1. Alcohol

2. Tobacco

3. Antiepileptic drugs (dilantin, valproic acid)

4. Thalidomide

Front 42

recurrence risk for cleft LP increases with:

(4)

Back 42

1. severity of trait

2. number of affected relatives

3. male fetus

4. how closely related the baby is to family member with cleft LP

Front 43

examples of cleft LP of syndromic origin:

(5)

Back 43

1. trisomy 13

2. 4p minus syndrome
(Wolf-Hirschhorn)

3. 22q deletion syndrome

4. Van der Woude syndrome

5. Native American myopathy

Front 44

2 features of trisomy 13:

Back 44

1, microcephaly

2. polydactyly

Front 45

trisomy 13 is severe;

Back 45

majority die during the first year

Front 46

22q deletion syndrome ~~

(3)

Back 46

1. split uvula (mild cleft)

2. hypocalcemia

3. learning disabilities/psychiatric disorders

Front 47

features of Van der Woude Syndrome:

(4)

Back 47

1. AD - that's why you want to test the parents

2. recurrence risk at 50%

3. single gene mutation in IRF6 gene on 1q

4. subtle - lip pits in parents suggest VdW

Front 48

4 features of NA myopathy:

Back 48

1. mut. in STACC3 gene

2. AR

3. club feet, other contractures

4. risk of malignant hyperthermia under gen. anesthesia
- and often NEED surgery too

Front 49

m.c. cause of Robin sequence =

Back 49

Stickler syndrome

Front 50

features of Stickler syndrome:

(3)

Back 50

1. vision problems

2. hearing problems

3. early arthritis

Front 51

cleft can also be caused by:

Back 51

amniotic bands

Front 52

inheritance of Marfan syndrome:

(2)

Back 52

1. AD

2. 25% de novo mut's

Front 53

incidence of Marfan =

Back 53

1 / 10,000

Front 54

features of Marfan:

(8)

Back 54

1. aortic root dilation/dissection

2. MVP

3. myopia, early-onset cataracts

tall stature with long, thin arms and legs, nl trunk

4. arachnodacytly (long, thin, “spider-like” digits)

5. scoliosis

6. pectus excavatum or carinatum
(hollow or pigeon chest)

7. pes planus (flat feet)

8. typical facies

Front 55

mut's of Marfan:

(3)

Back 55

1. allelic heterogeneity

2. various mutations within the FBN1 gene on chromosome 15q21

3. various mut's protein fibrillin

Front 56

dx of Marfan based on:

Back 56

phenotype

Front 57

management of Marfan:

(5)

Back 57

1. Cardiac features are life threatening - req. life-long follow-up.

2. B-blockers

3. annual ophthalmologic exams

4. no contact sports or strenuous activity

5. if preg, need to be careful about aortic dissection/rupture

Front 58

Leigh syndrome =

Back 58

progressive neurologic disease with motor and intellectual disability

due to mitochondrial

Front 59

features of Leigh:

(10)

Back 59

1. onset typically b/w 3-12 months, s/ts after viral illness

2. ~~ periods of deterioration followed by “plateaus” with stabilization of symptoms

3. poor suck

4. vomiting/irritability/failure to thrive, loss of head control, and loss of motor skills

5. sez's

6. hypotonia/muscle weakness/ataxia

7. eye problems

8. LA is often present during periods of deterioration

9. hypertintense lesions in the BS or BG on T2-weighted MRI

10. cardiac, hepatic or renal features.

~50% of individuals die by 3 years secondary to respiratory or cardiac failure

Front 60

incidence of Leigh =

Back 60

1 / 40,000 (all causes)

Front 61

inheritance of Leigh:

(3)

Back 61

1. locus heterogeneity

2. Mendelian (AD, X-linked)

3. or mitochondrial

Front 62

NARP =

Back 62

Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa

- retinitis starts as salt and pepper retinopathy

Front 63

features of NARP:

(5)

Back 63

1. childhood or YA onset

2. learning disabilities and developmental delays in child NARP

3. adult NARP ~ decline in ID

4. muscle weakness, ataxia, retinitis pigmentosum

5. mitochondrial inheritance

Front 64

relationship of MT-ATP6 gene to NARP and Leigh:

(3)

Back 64

1. mutant loads <60% are either asymp or have mild symptoms

2. ~70-90% have NARP

3. >90% have Leigh syndrome

Front 65

NF1 is dx'd on clinical symps - at least 2 of the following:

(6)

Back 65

1. 6 or more café au lait spots

2. 2 or more neurofibromas of any type or 1 plexiform neurofibroma

3. axillary or groin “freckling”

4. an optic glioma

5. 2 or more Lisch nodules (benign, raised iris hamartomas seen by slit lamp exam)

6. a 1st-degree relative with NF1

Front 66

CLS =

Back 66

cafe-au-lait spots

Front 67

features of NF1:

(6)

Back 67

1. progresses with age
(starts as CLS; Lisch nodules and cutaneous fibromas develop late childhood to adulthood)

2. some features are age-dependent

3. increased risk for learning problems (40-60%)

4. sez's

5. HTN (due to renal artery stenosis or rarely, pheo)

6. ~ malignant neoplasms

Front 68

incidence of NF1 =

Back 68

1 / 3000

Front 69

inheritance of NF1:

(3)

Back 69

1. AD

2. nearly complete penetrance, variable expression

3. 50% are de novo mut's

Front 70

mut. of NF1:

(3)

Back 70

1. NF1 gene,

2. chromosome 17q

3. prot. is neurofibromin

Front 71

gene testing for NF1:

(2)

Back 71

1. protein truncation testing,
sequencing,
FISH,
Southern blotting
=> 95% of

2. gene sequencing alone detects up to 89% of gene mut's

Front 72

management of NF1:

(6)

Back 72

1. complications increase with age

2. if severe intellectual disability present, it would be evident early

3. optic gliomas and progressive scoliosis in childhood

4. plexiform neurofibromas before adulthood.

5. surgical removal of neurofibromas generally not recommended unless compromising essential organ

6. first-degree relatives need examination

Front 73

genetic tests, in order from most broad to more specific:

(6)

Back 73

1. karyotype

2. FISH / 3. microarray

4. Sanger sequencing (single base and small microdeletions)

5. PCR (NT level)

6. all the other PCR-based approaches

Front 74

unique management of Turner =

(3)

Back 74

1. screen for celiac dz

2. HRT around puberty

3. if karyotype includes a Y chromosome cell line, increased risk for gonadoblastoma

Front 75

for a condition with MULTIPLE possible mutations (like CF), you want to do:

Back 75

DNA sequencing

Front 76

Hungtington dz =

Back 76

progressive disorder of cognition, motor, and psychiatric disturbance

Front 77

features of Huntington:

(6)

Back 77

1. motor symptoms include gait disturbance, progressive chorea, dysarthria

2. global decline in cognitive abilities occurs in ALL

3. significant personality changes affect 72%
(may include intermittent explosiveness, apathy, aggression, alcohol abuse, paranoia)

4. late stages: wt loss, total dependence, no speech, dysphagia

5. mean age of onset is 35-44
(10% have juvenile onset before age 21 with seizures and more rapid decline)

6. avg. age of death is 55 years
(suicide an issue)

Front 78

incidence of Huntington =

Back 78

3-7 / 100,000 of Western Europe descent

Front 79

genetics of Huntington:

(5)

Back 79

1. AD

2. CAG repeat within HD gene

3. above 60 repeats ~~ juvenile onset

4. repeat expansion tends to occur during paternal gametogenesis
=> juvenile Hunt. inherited almost exclusively from affected fathers

5. PCR