Bocian Clinical Syndromes

Question 1

What is triploidy

Answer 1

69 chromosomes

Question 2

Describe the chromosome constitution of triploidy

Answer 2

69,XXY - 60%
69, XXX - 35%
69, XYY - 5%

Question 3

Describe the etiology of triploidy

Answer 3

Most (65%) due to dispermy
Many (25%) due to fertilization with a diploid sperm (mitotic failure during meiosis)
Some (10%) due to fertilization with a diploid egg (failure to shed a polar body)

Question 4

Two types of Trisomy 21 genotype

Answer 4

47, XY, +21

47, XX, +21

Question 5

Down Syndrome is names for?

Answer 5

Dr. Langdon Down

Question 6

Symptoms of Down Syndrome

Answer 6

Intellectual disabilities, usually mild to moderate

Question 7

Typical physical features of down syndrome (6)

Answer 7

1. Up-slanting eyes
2. Small ears
3. Thin, down-turned lips
4. Short, broad hands
5. Single transverse palmar crease
6. 5th finger—single crease or short middle phalanx (middle segment)

Question 8

Describe the tone of Down Syndrome

Answer 8

Hypotonia (“low tone;” poor muscle tone; “floppiness”)

Question 9

Down syndrome organ dysfunction?

Answer 9

Congenital heart disease (45%)

Question 10

Lifespan for Down syndrome

Answer 10

Essentially normal lifespan if there is no serious heart disease or other complication

Question 11

Three types of chromosome abnormality in Down Syndrome

Answer 11

Nondisjunction
Translocation
Mosaicism

Question 12

Describe Down Syndrome Nondisjunction

Answer 12

Nondisjunction (3 separate copies of chromosome 21)

a) Most patients (95%) have trisomy due to nondisjunction

Question 13

Describe Down Syndrome translocation

Answer 13

Relatively few patients (3%) have translocations; t(14;21) is the most common—half are inherited,
half are de novo (occur for the first time in the patient); must do parents’ karyotypes to determine recurrence risk

Question 14

Describe Down Syndrome Mosaicism

Answer 14

Relatively few patients have mosaicism (2%)

Question 15

Describe recurrence risk of Down Syndrome

Answer 15

Recurrence risk depends on the mechanism (i.e., nondisjunction vs. de novo translocation vs. inherited translocation) and, in cases of nondisjunction, on the mother’s age at the time of the affected baby’s birth

Question 16

Trisomy 13 is called?

Answer 16

Patau syndrome

Question 17

Genotype for Trisomy 13

Answer 17

47, XY, +13

47, XX, +13

Question 18

Abnormalities of Trisomy 13

Answer 18

Multiple anomalies: cleft lip ± cleft palate, polydactyly (extra fingers or toes),
microphthalmia (small eyes), omphalocele, cardiac anomalies, renal anomalies, etc.

Question 19

Intellectual level of Trisomy 13

Answer 19

Severe intellectual disabilities

Question 20

Lifespan of Trisomy 13

Answer 20

Severely shortened lifespan (few reach past 6 months)

Question 21

Recurrence risk of Trisomy 13

Answer 21

Recurrence risk depends on the mechanism (i.e., nondisjunction vs. de novo translocation vs. inherited translocation) and, in cases of nondisjunction, on the mother’s age at the time of the affected baby’s birth

Question 22

Trisomy 18 is also called?

Answer 22

Edwards syndrome

Question 23

Trisomy 18 genotype

Answer 23

47, XY, +18

47, XX, +18

Question 24

Abnormalities of Trisomy 18

Answer 24

Clenched hand position and typical facial features

Question 25

Intellectual level of Trisomy 18

Answer 25

Profound intellectual diability

Question 26

Lifespan of Trisomy 18

Answer 26

Severely shortened lifespan, most die before 1 year

Question 27

Recurrence risk of Trisomy 18

Answer 27

Recurrence risk depends on the mechanism (i.e., nondisjunction vs. de novo translocation vs. inherited translocation) and, in cases of nondisjunction, on the mother’s age at the time of the affected baby’s birth

Question 28

Genotype of Turner syndrome

Answer 28

45,X

Question 29

Gender of Turner syndrome

Answer 29

Occurs only in females

Question 30

Phenotype of Turner syndrome

Answer 30

Physically and behaviorally female, even though they have only one “sex” chromosome

Question 31

Intelligence of Turner syndrome

Answer 31

Normal intelligence

Question 32

Stature of Turner syndrome

Answer 32

Short stature

Question 33

Describe gonads in Turner syndrome

Answer 33

Ovarian dysgenesis (“streak ovaries”) and infertility in most 1. Premature ovarian degeneration accounts for infertility 2. Most will not undergo puberty without hormone replacement

Question 34

Describe abnormalities of Turner syndrome

Answer 34

Fetal and congenital edema, cystic hygroma (a fluid-filled sac, usually over the neck), cardiac anomalies, renal anomalies, pedal edema (puffy feet) in the newborn

Question 35

Most Turner syndrome have genotype

Answer 35

45,X

Question 36

Recurrence of Turner syndrome

Answer 36

Unlikely

Question 37

Klinefelter syndrome genotype

Answer 37

47,XXY

Question 38

Gender of Klinefelter

Answer 38

Occurs only in males

Question 39

Phenotype of Klinefelter

Answer 39

Physically and behaviorally male

Question 40

Describe abnormalities of Klinefelter

Answer 40

Small testes without sperm; gynecomastia (breast enlargement); poor pubertal development without hormone replacement; tend to have relatively long limbs

Question 41

Virility of Klinefelter

Answer 41

Almost all are sterile

Question 42

Intellectual level of Klinefelter

Answer 42

earning disabilities,speech delays, and behavior disorders are common However, Data from postnatal diagnoses are artificially biased toward abnormality

Question 43

Recurrence risk of Klinefelter

Answer 43

Recurrence risk depends on the mother’s age at the time of the affected baby’s birth

Question 44

Describe 47, XXX gender

Answer 44

Physically and behaviorally female

Question 45

Appearance of 47, XXX

Answer 45

Normal appearance

Question 46

Intelligence of 47, XXX

Answer 46

Often low-normal intelligence or mild M.R., but many are normal; speech delays, and/or behavior difficulties common However, Data from postnatal diagnoses are artificially biased toward abnormality

Question 47

Empiric risk for trisomies is based on? Exceptions?

Answer 47

Empiric recurrence risk for trisomies (but not for XYY, Turner syndrome, or structural chromosomal anomalies) is based on the mother’s age at the time of the affected baby’s birth

Question 48

Cri du Chat is known as? Example of?

Answer 48

del 5p (Cri du Chat syndrome) – example of a deletion syndrome in which the deletion may be visible microscopically or may be submicroscopic

Question 49

Typical feature of del 5p?

Answer 49

Cat-like cry in infancy

Question 50

Intelligence of del 5p?

Answer 50

Intellectual disabilites

Question 51

Williams syndrome is an example of?

Answer 51

example of a microdeletion syndrome that is always submicroscopic

Question 52

Describe the microdeletion in Williams syndrome. What does it include?

Answer 52

Microdeletion of chromosome 7q11.23, including the elastin gene

Question 53

Describe the phenotype of Williams disease

Answer 53

Characteristic facial features Heart defects common (certain types more common than others) Hypercalcemia (abnormally high calcium in the serum)

Question 54

Describe the behavior of Williams syndrome

Answer 54

Characteristic behavioral/neurodevelopmental phenotype 1. Mild-moderate intellectual disabilities (language ability much better than cognitive ability) 2. Distinctive friendly, loquacious personality F. Recurrence is uncommon (<1%); rarely, the deletion

Question 55

Describe the tone of Prader-Willi syndrome

Answer 55

Severe congenital hypotonia (born with very low muscle tone; “floppy”) 1. Causes early, severe feeding difficulties

Question 56

Behavior of Prader-Willi

Answer 56

Typical behavioral phenotype | 1. As the hypotonia improves, they develop hyperphagia (severe overeating) and obesity

Question 57

Physical features of Prader-Willi

Answer 57

Mild, recognizable facial features 2. Relatively small hands and feet 3. Hypogenitalism (more recognizable in males) 4. Short stature 5. Cognitive impairment, usually mild intellectual disabilities 6. Behavioral disorders

Question 58

Describe the etiology of Prader-Willi

Answer 58

Cytogenetic or molecular abnormality at 15q11-q13 with abnormal DNA methylation analysis a) Deletion involving the paternally-inherited 15q b) Maternal uniparental disomy (i.e., both #15’s were inherited from the mother and none from the father)

Question 59

Describe recurrence of Prader-Willi

Answer 59

Rare Higher risk if imprinting control element is at fault Lesser risk if chromsomal translocation has occured Minimal risk if from a deletion or uniparental disomy

Question 60

Tone of Angelman syndrome

Answer 60

Jerky, “puppet-like” gait; poor balance

Question 61

Physical characteristics of Angelman

Answer 61

Microcephaly | Seizures

Question 62

Intellectual level of Angelman

Answer 62

Severe intellectual diabilities

Question 63

Behavior of Angelman?

Answer 63

Appear unusually happy

Question 64

Etiology of Angelman

Answer 64

Cytogenetic or molecular abnormality at 15q11-q13 with abnormal DNA methylation study a) Deletion involving the maternally-inherited 15q b) Paternal uniparental disomy for #15 (5%) (i.e., both #15s were inherited from the father and none from the mother)

Question 65

Angelman mutation?

Answer 65

7% or so have mutation in UBE3A gene

Question 66

Recurrence risk of Angelman

Answer 66

Depends on mechanism

Question 67

DiGeorge/Velocardiofacial syndrome is known also as?

Answer 67

22q11.2 deletion syndrome

Question 68

Characteristics of DiGeorge

Answer 68

Markedly variable physical features, but some common patterns 1. Cleft palate 2. Heart anomalies common, especially defects of conotruncal development of isolated conotruncal cardiac anomalies 3. Often have characteristic facial features; a variety of other anomalies 4. Immune deficiencies 5. Hypocalcemia (abnormally low serum calcium); due to hypoparathyroidism (poor function of the parathyroid gland, which regulates calcium level)

Question 69

Intelligence of DiGeorge

Answer 69

Learning disabilities or mild or moderate intellectual disabilities common, but many have normal intelligence

Question 70

Recurrence risk of DiGeorge

Answer 70

Recurrence risk depends on whether the deletion was inherited or occurred de novo in the patient Need to test parents even if normal (7% have deletion)