microdeletion syndromes

Question 1

3 clinical features associated with 16p11.2 deletion syndrome

Answer 1

macrocephaly, developmental delay, ASD, siezures (20%)

Question 2

3 clinical features of Angelmans syndrome

Answer 2

Severe mental retardation or developmental delay
Absent speech
Happy smiling disposition with inappropriate laughter
Ataxic gait with flapping upheld arms (originally known as the “happy puppet” syndrome)
Microcephaly, large wide open mouth, prominent chin, deep set eyes & protruding tongue, tongue thrusting, drooling and mouthing
Love of water
Hypopigmentation
Hypo- and and hypertonia are also seen
Early onset epileptic seizures

Question 3

gene location of PWS/AS

Answer 3

15q11.-q13

Question 4

clinical features of PWS

Answer 4

Disorder of growth and development
Severe neonatal hypotonia (“floppy” baby) & feeding difficulties and/or failure to thrive in infancy
Hyperphagia resulting in obesity (diabetes & cardiac failure) in later infancy/early childhood
Mild-moderate MR, developmental delay & behavioural disorders (stubbornness, temper tantrums, poor peer interactions, unusual skill with jigsaw puzzles)
Characteristic facial features: almond-shaped eyes, low set ears, down-turned mouth, bilateral epicanthal folds
Short stature, small hands and feet
Hypogonadism in both males & females
Hypopigmentation
Skin picking

Question 5

Features of 1p36 deletion syndrome

Answer 5

DD, dysmorphic, hypotonia, NO speech, behaviour probe-biting,tantrums, increase risk neural crest tumours, late Fontanelle closure

Question 6

% 1p36 deletion syndrome that is inherited from balanced parental rea

Answer 6

20%

Question 7

What locus does TAR map to?

Answer 7

1q21

Question 8

How does TAR arise?

Answer 8

LCRs blocks X 4. Class 1: distal smaller and class 2: larger TAR and distal region

Question 9

What syndromes are located at 1q21

Answer 9

TAR- proximal, distal 1q21 deletion, 1q21 duplication

Question 10

Features of 1q21 dup syndrome

Answer 10

Macrocephaly, TOF incomplete penetrance

Question 11

Candidate gene for head size in 1q21

Answer 11

HYDIN2. Del:small and dup:large

Question 12

Phenotype of TAR

Answer 12

Absent radii WITH thumbs, cows milk intolerance, MDT

Question 13

Genetics of TAR

Answer 13

Common 200kb deletion, 11genes, proposed 2nd hit required?

Question 14

Where is mowat Wilson syndrome

Answer 14

2q22 deleted

Question 15

Phenotype of mowat Wilson

Answer 15

Dysmorphic-open mouth, pointy chin, heart abns, aGenesis corpus callosum, Genito urinary problem

Question 16

Mowat Wilson candidate gene

Answer 16

ZEB2. Mutations and deletions,2% gene disruption due to Chr rea. Most de novo

Question 17

Where is Albright like syndrome located and what causes it (del/dup)?

Answer 17

2q37 (deletion)

Question 18

Albright like syndrome candidate gene

Answer 18

Hdac4

Question 19

Phenotype of Albright like syndrome

Answer 19

DD, autism,behavioural, dysmorphic, skeletal abns,GR. Phenotype variable and not correlate with deletion size

Question 20

Features of 2q37 duplication

Answer 20

No dysmorphism and normal IQ

Question 21

Genetics of ALports syndrome (hereditary nephritis)

Answer 21

X linked col4a5 mutation, or autosomal recessive col4a3 and col4a4 mutations (Chr 2). Genes involved in collagen biosynthesis

Question 22

Phenotype of alports

Answer 22

Kidney disease, hearing loss, eyes-cataracts, bloody urine and protein in urine.

Question 23

What does VHL stand for?

Answer 23

Von hippel lindau

Question 24

Locus for VHL

Answer 24

3p25-26

Question 25

Origins of WHS

Answer 25

90% are de novo. Deletions 55%, unbalced translocation 40-45%, complex rea in few. Can be Inherited from female carriers of t(4;8)(p16.3;p23). Others male derived.

Question 26

Phenotype of WHS

Answer 26

Dysmorphism Greek warrior helmet, GR, seizures, MR, psychomotor delay

Question 27

Is there a correlation of deletion size and phenotype severity

Answer 27

Increase size usually = increased severity. Arrays have identified more due to cryptic unbalanced reas which may explain variability south et al 2008

Question 28

Genes in WHSCR and phenotype links

Answer 28

Whsc1 (face, GR)and letm (seizures)

Question 29

Incidence of cri du chat

Answer 29

1/50,000

Question 30

Where is cri du chat critical region

Answer 30

5p15.3 -15.2

Question 31

What micro deletion is at 7q11.23

Answer 31

Williams

Question 32

Incidence of Willian's syndrome

Answer 32

1/10,000

Question 33

Key gene in ws deletions

Answer 33

Eln - elastin

Question 34

Where is SOTOS (cerebral gigantism)

Answer 34

5q35

Question 35

Inheritance pattern of SOTOS

Answer 35

Autosomal dominant

Question 36

Genetic abnormalities seen in SOTOS

Answer 36

95% de novo. Mainly mutations but is a recurrent Japanese 1.9Mb deletion.

Question 37

Phenotype of SOTOS

Answer 37

Excessive growth up to age 3, macro exhale large hands and feet, increased bone age, mild-severe LD, cranial abns, large long skull, high bossed forehead

Question 38

Where is the Twist gene and what is associated syndrome

Answer 38

7p21.1 involved in saethre chotzen syndrome. Point mutations or deletions seen- inc penetrance

Question 39

Phenotype saethre chotzen syndrome

Answer 39

Skull defect prem fusion of cranial bones which prevents normal growth and results in odd shape/asymmetric skull, normal IQ

Question 40

Where is shfm ectrodactyly locus

Answer 40

7q21.3

Question 41

Where is shh gene located and what do defects in it cause

Answer 41

7q36, holoprosencephaly

Question 42

Where are OR gene clusters

Answer 42

8p23.1

Question 43

Why is there such a high incidence of OR reas?

Answer 43

Repd (distal rpt) and repp (prox repeat) flank 5Mb region

Question 44

Which genes associated with langer Gideon

Answer 44

Trsp1 and ext1 (multiple exotoses type1)

Question 45

CDC phenotype

Answer 45

Cat cry microcephaoy seizure severe mr fertile hypotonia

Question 46

Where is region deleted in Alfi's syndrome

Answer 46

9p22.3

Question 47

Phenotype of Alfi's syndrome

Answer 47

Trigonocephaly, severe speech probs, mr, abn genitalia dysmorphic

Question 48

Where is DGS-2

Answer 48

10p13

Question 49

Phenotype of DGS-2

Answer 49

More severe than DGS. Hypoglycaemia, absent thymus-> T cell deficit, heart, ,male abn genitalia, mr, dysmorphism

Question 50

Percentages of different types I | Of patau syndrome

Answer 50

75%: NDJ. Most mat meiosis 1 or mitotic. 20% unbalanced rob. 5% mosaic

Question 51

Phenotype 13q14 deletion syndrome

Answer 51

Depends on size. Retinoblastoma, DD, speech language delay, dysmorphic

Question 52

What is wang syndrome

Answer 52

Upd14 pat. More severe than mat upd14. Dysmorphic, mr, abdominal wall defect

Question 53

Where is rubenstein taybi locus and associated gene

Answer 53

16p13.3. CREBBP

Question 54

R-T phenotype

Answer 54

Generalised disregulation of gene expression of CREBBP causes multiple abns. Short, mr, dysmorphic, broad thumb/big toe, increased cancer risk

Question 55

Miller dieker locus

Answer 55

17p13.3

Question 56

SMS locus

Answer 56

17p11.2

Question 57

Duplication of 17p11.2

Answer 57

Potaki-lupski. ID by aCGH in 2008

Question 58

Phenotype potaki-lupski

Answer 58

DD, autism, FTT

Question 59

Cyto abnormality seen in Emmanuel syndrome

Answer 59

Der(22)t(11;22)(q23.3:q11.2)

Question 60

Phenotype of CAt eye syndrome

Answer 60

Ocular Coloboma, anal abns, septal heart defects, dysmorphism,skin tags. No obvious differences between types 1 and 2

Question 61

Region associated with phelan-mcdermid syndrome

Answer 61

22q13 deletion

Question 62

Which are the 2 most common terminal micro deletions?

Answer 62

1p36 and then 22q13

Question 63

Phenotype of 22q13 deletion

Answer 63

Dysmorphic, DD.speech delay, hypotonia