Chromosomal Disorders

Question 1

List the microdeletions/duplications and LCRs for chromosome 15

Answer 1

15q11.2 del/dup BP1-2

15q11q13 PWSAS/ dup BP 1-3 (2-3)

15q13.3 del/dup BP4-5 (3-5)

Idic(15q) ?BP3,4,5

15q24 micro deletion LCR15q24 B-C

(Also Blooms: 15q26.1: not NAHR)

Question 2

Which chr 15 recurrent abns show incomplete penetrance/variable expressivity

Answer 2

15q11. 2 del/dup BP1-2

15q13. 3 del/dup BP4-5

Question 3

Which chr 15 recurrent abns are associated with seizures/epilepsy

Answer 3

Idic(15q). Angelmans. 15q13.3 microdel/dup

??15q11.2 BP1-2

Question 4

What are the 3 clinical features for 15q24 microdeletion. Include size and a gene

Answer 4

Growth delay. ID. ASD. Dysmorphism.

1.7-6.1Mb. CYP11A1, SEMA7A

Question 5

What are the 3 clinical features for 15q11q13 microduplication.

Answer 5

Reciprocal to AS/PWS. Always maternal in origin.

LD. ASD. seizures. Motor delay. Hypotonia. Sleep disturbances

Question 6

What possible causes of variable expressivity are there

Answer 6

1) an additional cnv contributing to the phenotype.
2) SNP in remaining allele affecting possible thresholds of production/ compound heterozygote.
3) epigenetic changes.
4) modifier genes effecting function of remaining allele

Question 7

Which chr 16 recurrent abns show incomplete penetrance/variable expressivity

Answer 7

16p13. 11 del/dup.
16p12. 2 del/dup
16p11. 2 distal del
16p11. 2 proximal del/dup

Question 8

What are the 3 clinical features for 16p13.11 microduplication . Include size and a gene

Answer 8

1.65Mb 22genes MYH11. NDE1. IP/VE

Dev and speech delay. ASD, ADHD. Schizophrenia. FTAAD (MYH11)

Question 9

What are the 3 clinical features for 16p13.11 micro deletion . Include size and a gene

Answer 9

1.65Mb 22genes MYH11. NDE1. IP/VE

Dev del. ID. ASD. epilepsy (LIS1-NDE1). ?schizophrenia (DISC1-NDE1). Dysmorphism.

Question 10

What are the 3 clinical features for 16p12.2 microdel/dup. Include size and a gene

Answer 10

520Kb (2x68KB segmental dups). IP/VE. CDR2.

Dev and speech delay. ID. ASD, ADHD. seizures. Schizophrenia.

Question 11

What are the 3 clinical features for 16p11.2 distal microdeletion. Include size and a gene

Answer 11

220Kb. BP2-3. SH2B1. IP/VE

Dev del. ID. Severe early onset obesity. Seizures. Behavioural problems.

Question 12

What are the 3 clinical features for 16p11.2 proximal del/dup. Include size and a gene

Answer 12

600Kb BP4-5 (2x147Kb SD). TBX6.

Del: Dev, motor, language delay. ID. seizures. ASD.,ADHD.

Dup: highly variable phen w. Asymptomatic carriers. motor del. ID. ASD. ADHD. Microcephaly. Schizophrenia.

Question 13

What are the 3 clinical features for 17q21.31 micro deletion. Include size and a gene

Answer 13

500-650Kb. 1/16,000. KANSL1, MAPT, CRHR1

MR. Mild-mod ID. Seizures. Hypotonia. Motor delay. CHD. Skin pigmentation. Cryptorchidism. Hypospadias. Duplex kidney. Dysmorphism.

Question 14

What are the 3 clinical features for 17q21.31 microduplication.

Answer 14

ID. Microcephaly. Mild dysmorphism. ASD.

Question 15

Name 3 features of T22/mT22

Answer 15

Microcephaly. Micrognathia. Webbed neck. CHD. Renal anomalies. Hemidystrophy.

Question 16

What is the causes of phenlan mcdermid and clin features

Answer 16

75% dn del. 20% unbalanced rearra. 4% dn unbalanced rearr. Less than 1% SHANK3 mut

Neonatal hypotonia. Macrocrania. ASD. Dev del with absent speech.

Question 17

What the recurrence risk Emmanuel syndrome

Answer 17

3.7% female. Lees than 0.7% males

Question 18

Describe mecp2 duplication syndrome

Answer 18

300kb-4mb Xq28 dup. Affects males (100% penetrant)

Severe mr. Absent speech. Infantile Hypotonia. Progressive Spasticity, seizures, recurrent infections.

Question 19

Describe Rett syndrome

Answer 19

Mecp2 mut. Affects females.

Progressive neurodevelopmental disorder. Normal devp until 18 months then regress. Hallmark: hand flapping. Seizures. Ataxic gait. Loss of speech. Autistic like behaviour: crying, panic attacks.

Diff diag:AS