Imprinting Disorders Flashcards
Chromosomes where imprinting may occur
6, 7, 11, 14, 15, 16
Russell-Silver Syndrome
Mode of imprinting: Maternally imprinted, paternally expressed
Caused by: Can occur due to postzygotic imprinting defects on 11p15.5 (leads to hypomethylation on paternal chromosomes at IC1 affecting genes IGF2 and H19 – REMEMBER THAT THESE GENES ARE DAD’S “MAKE THE BABY BIG AND EVOLUTIONARYILY COMPETITIVE” GENES) or due to MATERNAL UPD 7
Major features:
- Triangular face shape with delicate facial features
- Small for gestational age/low birth weight
- Hypoglycemia
- Excessive sweating, especially at night (may be due to hypoglycemia)
- Developmental delay
- Learning disabilities
- Blue sclera in childhood
- Body asymmetry
- GI complications – constipation
- Precocious puberty
Beckwith-Widemann Syndrome
Mode of Imprinting: Paternally imprinted, maternally expressed
Critical region: 11p15
Caused by: Paternal UPD, Maternal rearrangements involving 11p15, abnormal methylation of 11p15 (imprinting defect), mutation in maternal CDKN1C
Testing: Methylation studies of 11p15 (loss or gain of methylation at different imprinting centers on the maternal chromosome), UPD cytogenetic studies
Major features:
- Overgrowth syndrome
- Macrosomia
- Ear lobe creases, helical ear pits
- Macroglossia (enlarged tongue)
- Omphalocele
- Visceromegaly of intra-abdominal organs
- Increased risk for embryonic tumors: Wilms tumor, hepatoblastoma, neuroblastoma: Test for using regular AFP testing (discontinue around age 4, risk drops)
- Renal abnormalities
- Cytomegaly of the fetal adrenal cortex
- Cardiomegaly/Cardiomyopathy
Minor features:
- Polyhydramnios
- Neonatal hypoglycemia
- Vascular malformations (facial nevus flammeus)
- Structural heart defects
- Diastasis recti
- Advanced bone age
Angelman Syndrome
Mode of Imprinting: Paternally imprinted, maternally expressed
Critical region: 15q11.2-q13, UBE3A
Caused by: Paternal UPD, maternally inherited UBE3A mutations, maternal deletions, imprinting defect of maternally inherited chromosome
Major features:
- “Happy puppet syndrome”
- Severe developmental delay beginning at 6-12 months
- Limited or absent speech
- Ataxia
- Laughter and smiling, excitability
- Hand flapping
- Seizures
- Dysphagia
- Flexed arms during ambulation
- Fascination with water, crinkly items
Prader-Willi Syndrome
Mode of Imprinting: Maternally imprinted, Paternally expressed
Critical region: 15q11.2-q13
Caused by: Maternal UPD, paternal deletion
Major features:
- Hypotonia and failure to thrive in neonatal/early development
- Global developmental delay
- Excessive eating (including eating non-food items)
- Obesity
- Mild intellectual disability
- Hypogonadism
- Hypothyroidism
- Sleep abnormalities
- Behavioral problems
