Angelman Syndrome Flashcards Preview

SB_Genetics (Pediatrics Royal College 2018) > Angelman Syndrome > Flashcards

Flashcards in Angelman Syndrome Deck (10)
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1
Q

What type of genetic disorder is Angelman?

A

Disorder of imprinting = Uniparental disomy, deletion of MATERNAL copy

65-70% microdeletion MATERNAL chromosome 15q11.2-q13
3-7% paternal uniparental disomy chromosome 15 (milder phenotype)
3% imprinting center defect within maternal 15q11.2-q13
5-11% UBE3A gene mutation
10-15% unknown mechanism

2
Q

What is the most sensitive single test for Angelman Syndrome?

A

DNA methylation

DNA sequence analysis required to identify UBE3A

3
Q

What is the recurrence risk for microdeletion and paternal uniparental disomy?

A

<1%

4
Q

What is the recurrence risk for maternally inherited imprinting center defect or UBE3A mutation?

A

50%

5
Q

What are the associated medical findings with Angelman Syndrome?

A
  1. Non-specific psychomotor delay and/or seizures
  2. Speech delay
  3. GDD
  4. Abnormal forward gait, arms held high, flexed at elbows
  5. Truncal hypotonia, hypertonic limbs
  6. Tremulous, jerky
  7. Feeding/growth problems
  8. Acquired microcephaly (<2SD below mean)
6
Q

What are the developmental outcomes of Angelman Syndrome?

A
  1. Intellectual disability (usu. severe to profound, 24-30m average cognitive skills)
  2. Receptive language is a relative strength
  3. Typically non-verbal with good social skills as adults (good non-verbal social communication)
  4. Persistent SPONTANEOUS social smiling (1-3m) and fits of laughter (can be as early as 10wks)
  5. Truncal hypotonia (hypertonic in limbs)
  6. Commando crawl - not on all fours
  7. Hand flapping with excitement
  8. LOVE water, open mirrors, music toys
  9. Cartoons are scary
  10. Hyperactive, inattentive
  11. Oral exploration
  12. Abnormal sleep cycles
7
Q

What is the DDx for seizures and GDD?

A
  1. Metabolic
  2. CNS embryologic developmental abnormality
  3. Genetic epilepsy syndromes
8
Q

What is the DDx for Angelman Syndrome?

A
  1. Rett syndrome
  2. Autism
  3. Ataxia CP
  4. Mowat-Wilson syndrome
  5. Alpha Thalassemia-Intellectual Disability Syndrome (X-linked)
  6. Pitt-Hopkins Syndrome
9
Q

What are the recommendations for Angelman Syndrome?

A
  1. Anticonvulsants - peds neurology
  2. Peds ophthalmology
  3. Early intervention
  4. Adaptive equipment as needed
  5. Structured environment
  6. Family support for abnormal sleep-wake cycles and hyperactivity (very few children require stimulants or sleep aides)
10
Q

What are the major clinical manifestations of Angelman syndrome?

A
1. Developmental delay
2 Lack of speech
3. MR
4. Abnormal gait
5. Seizures
6. Acquired microcephaly
7. Hypopigmentation