Methylation

Question 1

[Gen/Methyl/SRS]

Genetic causes of Silver-Russell syndrome? (2)

Answer 1

1. Hypomethylation of imprinting control region 1 (ICR1) at 11p15.5 (35-50%)
2. Maternal uniparental disomy (7-10%)

Question 2

[Gen/Methyl/SRS]

Characteristics of Silver-Russell syndrome? (4)

Answer 2

1. Pre/post-natal low weight and height (normal HC or relative macrocephaly)
2. Delayed bone age
3. GI reflux
4. Cafe au lait spots

Question 3

[Gen/Microdel/PWS]

Prader-Willi syndrome treatment in the first year? (2)

Answer 3

1. Nutrition management
2. Growth hormone: universal growth hormone deficiency in PWS

Question 4

[Gen/Microdel/PWS]

Genetic causes for Prader-Willi (2)

Answer 4

1. Inheritance of paternal deletion of 15q11.2-q13
2. Maternal uniparental disomy (only maternal copies)

Question 5

[Gen/Microdeletion/AS]

Genetic mechanisms of Angelman syndrome (2)

Answer 5

1. Inheritance of maternal deletion of 15q11.2-q13
2. Paternal uniparental disomy, only parental copies

Question 6

[Gen/Microdeletion/PWS]

Infancy characteristics of Prader-willi syndrome (3)

Answer 6

1. Hypotonia
2. Feeding difficulties
3. Facial: Narrow forehead, Almond-shaped eyes

Question 7

[Gen/Microdeletion/PWS]

Childhood characteristics of Prader-Willi (6)

Answer 7

1. Hyperphagia
2. Short stature
3. Small hands/feet
4. Hypogonadism
5. Behavior disorders
6. Mild intellectual disability

Question 8

[Gen/Microdel/AS]

Neurologic characteristics of Angelman syndrome (7)

Answer 8

1. Seizures
2. Severe intellectual disability
3. Microcephaly
4. Ataxia
5. Hand-flapping behaviors
6. Outbursts of laughter
7. Puppet-like gait

Question 9

[Gen/Methyl/BWS]

Characteristics of Beckwith-Wiedemann syndrome (6)

Answer 9

1. Growth disorder (neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia)
2. Omphalocele
3. Embryonal tumors (Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma)
4. Visceromegaly, adrenocortical cytomegaly
5. Renal abnormalities (medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly)
6. Ear creases/pits

Question 10

[Gen/Methyl/BWS]

Most common genetic cause and percentage of Beckwith-Wiedemann syndrome? (2)

Answer 10

1. Loss of methylation on the maternal chromosome at imprinting center 2 (IC2) in 50% of affected individuals
2. Paternal uniparental disomy for chromosome 11p15 in 20%

Question 11

[Gen/Methyl/BWS]

Embryonal tumor associated with Beckwith-Wiedemann syndrome? (4)

Answer 11

1. Wilms tumor
2. Hepatoblastoma
3. Neuroblastoma
4. Rhabdomyosarcoma