clinical vignettes

Question 1

cause of down syndrome

Answer 1

1. trisomy 21 (95%)
2. unbalanced translocation between 21 and another afrocentric chrome (3-4%)
3. mosaic tri 21 (1-2%)

Question 2

Trisomy 21 is unbalanced translocation between

Answer 2

chromosome 21 and another afrocentric chromosome

important to check karyotype of parents

Question 3

trisomy 21, 95% of patients with

Answer 3

down syndrome
parents usually have normal chromosomes
recurrence risk is 1:100

Question 4

mosaic trisomy is

Answer 4

mixture of norma cells and cells containing trisomy 21
1-2% of down syndrome
phenotype tends to be more mild

Question 5

approach to prenatal counseling in DS

Answer 5

1. caused by error of nondysjunction
2. increasing risk with increasing maternal age
3. prenatal screening

Question 6

DS first trimester screening:

Answer 6

detects 82-87%
ultrasound measurement of nuchal fold +B-hCH (human chorionic gonadotropin) + PAPP-A (pregnancy-associated plasma protein A)

Question 7

DS second semester screeing:

Answer 7

-detection rate 80%
-quad screen-hCG (human chorionic gonadotropin), AFP (α-fetoprotein), unconjugated estriol, and inhibin level
– Suspicion of DS based on 1st or second trimester screening can by confirmed by chromosome analysis via amniocentesis or CVS (chorionic villus sampling)

Question 8

– Detection rate of 1st trimester + second trimester screening =

Answer 8

95%

Question 9

increased risk of trisomy with

Answer 9

advanced maternal age

Question 10

PW Presentation in newborn period

Answer 10

hypotonia and

dysmorphic features, undescended testicles.

Question 11

PW diagnosis made by

Answer 11

Diagnosis can be made with FISH or microarray

marker on chromosome 15, SNRPM deletion

Question 12

PW symptoms:

Answer 12

-early failure to thrice and feeding difficulties
-preschool age hyperphagia and weight gain
-ophthalmologic problems
strabismus and nystagmus

Question 13

PW treatment

Answer 13

growth hormone to help control obesity and improve short stature

Question 14

Deletion on Paternal chromosome 15 results in

Answer 14

prader willi

Question 15

deletion on maternal chrom 15 results in

Answer 15

angelman’s syndrome

Question 16

Prader-Willi Syndrome results when genetic information is missing from ______

Answer 16

the paternal allele of 15q11-q13.

This region of chrm 15 is imprinted

Question 17

PWS can be caused from

Answer 17

deletion of paternal allele or

uniparental disomy of the maternal allele

Question 18

PWS testing:

Answer 18

The maternal and paternal alleles are marked by different patterns of methylation. Therefore, methylation testing of this chromosome is one way to diagnose PWS or Angelman syndrome. If a deletion is present, a FISH test or a miccroarray can be done to confirm the diagnosis.

Question 19

PWS infancy:

Answer 19

1. hypotonic
2. almond shaped eyes
3. undescended testicles
4. severe feeding problems which often necessitate placement of a feeding (Gtube) gastrostomy tube. 5. lighter pigmentation

Question 20

Toddler/Preschooler:

Answer 20

1. feeding problems completely reverse, and the child will eat anything and everything, without ever feeling sated.
2. very obese, unless treated with growth hormone.

Question 21

PWS: Common Medical Issues:

Answer 21

1. Eyes: strabismus, nystagmus common
2. Orthopedics: scoliosis is common
3. Respiratory: obstructive sleep apnea
4. Developmentally: mild-moderate cognitive disabilities, behavioral issues

Question 22

Linkage disequilibrium between patients with Autism and polymorphisms in the _________ have been reported. _________ is an important neurotransmitter in the CNS.

Answer 22

GABAA –b3 locus on chromosome 15q

γ-aminobutyric acid type-A

Question 23

_________
chromosome anomalies are one of the most frequently reported cytogenetic
abnormalities in patients with autism

Answer 23

Maternally derived proximal 15q11-q13

Question 24

15q interstitial duplication

Answer 24

A piece of a chromosome can be copied, resulting
in a duplication or partial Trisomy (in this picture,
the duplication is an
interstitial duplication
in the middle of the chromosome

Question 25

Angelman Syndrome etiology:

Answer 25

5q deletion in PWS/AS region from maternal allele, detected with FISH, UPD of 15q, or imprinting errors of 15q detected with methylation studies

Question 26

angelman syndrom symptoms

Answer 26

mildly dysmorphic facial features, hypotonia in infancy spasticity in older patients, Intellectual Disability (ID), seizures, autism

Question 27

Chrom abnormalities in 15 cause:

Answer 27

1. PWS: paternal deletion 2. Angelman syndrome: maternal deletion 3. IDIC 15: associated with autism/hypotonia/seizures/ID 4. Maternally inherited interstitial duplication: associated with autism/hypotonia/seizures/ID

Question 28

Causes of down syndrome

Answer 28

1. Trisomy 21: 95% 2. Unbalanced Translocation between chromosome 21 and another acrocentric chromosome: 3-4% 3. Mosaic Tri 21(mixture of normal cells and cells containing Tri 21): 1-2 %

Question 29

3 kinds of trisomy associated with live births

Answer 29

13, 18, 21

Question 30

infants with DS

Answer 30

``` – Growth parameters normal – midfacial hypoplasia – upslanting palpebral fissures – small ears – large-appearing tongue – low muscle tone, -- increased joint mobility – short fingers, --transverse palmar crease*, Vth finger incurving (clinodactyly), increased space between toes 1 and 2 ```

Question 31

DS common medical issues

Answer 31

1. cardiac issues 2. Gastrointestinal 3. Ophthalmologic 4. Ear, Nose, Throat Problems 5. Endocrine problems 6. Orthopedic problems 7. Hematologic issues 8. developmental 9. Neurologic 10. Psychiatric

Question 32

DS Cardiac issues

Answer 32

– Seen in approximately 50% of patients with DS – All types of anomalies may be present, but Atrioventricular Canal is common to DS – Echocardiogram in the newborn period is recommended

Question 33

DS Gastrointestinal

Answer 33

``` – 10-15% of infants have structural anomalies 1. Esophageal atresia 2. Duodenal atresia 3. Hirschsprung’s – functional GI issues 1. Feeding problems 2. constipation 3. GERD 4. Celiac Dz ```

Question 34

DS Ophthalmologic problems

Answer 34

1. blocked tear ducts 2. myopia 3. lazy eye 4. Nystagmus 5. Cataracts

Question 35

DS-- Ear, Nose and Throat

Answer 35

1. chronic ear infections 2. Deafness – both sensorineural and conductive – chronic nasal congestion 3. enlarged tonsils and adenoids 4. obstructive apnea

Question 36

DS: Endocrine Problems

Answer 36

1. Thyroid dz – most commonly hypothyroidism 2. Insulin Dependent Diabetes – Alopecia Areata 3. reduced fertility (but normal puberty)

Question 37

DS: Orthopedic Problems

Answer 37

1. hips 2. Joint subluxation 3. atlantoaxial subluxation

Question 38

DS Hematologic problems

Answer 38

1. Myeloproliferative disorder in newborn 2. increased risk of leukemia 12-20x 3. iron deficiency anemia

Question 39

DS developmental problems

Answer 39

Psychiatric problems Depression Early Alzheimer's Autism= 1/10

Question 40

Turner syndrome karyotype

Answer 40

XO

Question 41

Turner's syndrom CVS abnormailites

Answer 41

1. bicuspid aortic valve 2. Coarctation of aorta 3. systemic hypertension 4. prolonged QTc syndrome 5. Partial anomalous pulmonary venous connection 6. Persistent left SVC

Question 42

Turner's syndrome eye abnormalities

Answer 42

1. inner canthal folds 2. ptosis 3. blue sclera

Question 43

Turner syndrom skeletal abnormalities

Answer 43

1. cubitus valgus 2. short 4th metacarpal 3. short stature

Question 44

Turner syndrom neck

Answer 44

1. webbed neck 2. low hairline 3. cystic hygroma

Question 45

Turner syndrome learning abnormalities

Answer 45

1. difficult in math 2. visual spatial skills 3. low non verbal scores

Question 46

effective health outcome =

Answer 46

patients culture +physicians culture

Question 47

Turner's syndrome: challenges across lifespan

Answer 47

1. infertility 2. stature 3. sexual development 4. concerns regarding health and aging

Question 48

Turner's syndrome: common pitfalls in disclosure

Answer 48

1. secret keeping 2. difficulty communicating an infertility diagnosis 3. perceived negative experiences with physicians