- * Dr. Angelman used the term "Happy Puppet Children" to describe children with Angelman because it combines their happy demeanor and stiff/jerky movements; he reportedly conjured this term after seeing the painting "Boy with a Puppet" at the Castelvecchio Museum in Verona.
- Additional key clinical characteristics include microcephaly, seizures, and severe speech abnormalities (generally a lack of speech).
Angelman Syndrome
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Genetics
- Majority of cases are from deletions in the chromosome 15 q11-q13 region on the MATERNAL inherited chromosome.
- E3 ubiquitin protein ligase (UBE3A) gene deletion is the most common cause of Angelman syndrome
- Minority of cases are from paternal uniparental disomy.
- In a minority of cases, there isn't a deletion on the maternal chromosome 15 but rather those genes simply aren't inherited from the mother (both copies of the genes are inherited from the father). This is referred to as paternal uniparental disomy.
- See Genomic Imprinting & Uniparental Disomy
Universal Clinical Manifestations
- Happy Demeanor
- Prominent smiling and enthusiasm
- Inappropriate laughter/easily excitable
- Stiff/Ataxic movements
- Tremulous and jerky movements of the limbs
- Flap hands when walking
- "Happy Puppet Children"
- Dr. Angelman used the term "Happy Puppet Children" to describe children with Angelman because it combines their happy demeanor and stiff/jerky movements; he reportedly conjured this term after seeing the painting "Boy with a Puppet" at the Castelvecchio Museum in Verona.
- Lack of speech (or paucity of speech)
- Use gesturing for communication
Common Clinical Manifestations
- Stereotypies
- Fascination with water-related items and crinkly items
- Hypopigmentaion of hair, skin, eyes
- Microcephaly (80% of patients)
Cognitive Impairment
- Generally, severe intellectual disability
Epilepsy
- Usually before age 3
- In > 80% of patients
- Various EEG patterns
- Frequently: High amplitude, rhythmic 2-3 Hz frontally-based activity with intermittent epileptiform discharges
Diagnosis
- Methylation analysis with fluorescence in situ hybridization (FISH) or chromosomal microarray (CMA).
References
- “Angelman Syndrome - NORD (National Organization for Rare Disorders).” NORD (National Organization for Rare Disorders) (blog). Accessed May 11, 2018. https://rarediseases.org/rare-diseases/angelman-syndrome/.
- Butler, Merlin G., and Travis Thompson. “Prader-Willi Syndrome: Clinical and Genetic Findings.” The Endocrinologist 10, no. 4 Suppl 1 (July 2000): 3S-16S.
- Cortés M, Fanny, Alliende R, M. Angélica, Andrés Barrios R, Bianca Curotto L, Lorena Santa María V, Ximena Barraza O, Ledia Troncoso A, Cecilia Mellado S, and Rosa Pardo V. “Caracterización Clínico-Genético-Molecular de 45 Pacientes Chilenos Con Síndrome de Prader Willi.” Revista Médica de Chile 133, no. 1 (January 2005): 33–41. https://doi.org/10.4067/S0034-98872005000100005.
- Dan, Bernard. “Behavior and Neuropsychiatric Manifestations in Angelman Syndrome.” Neuropsychiatric Disease and Treatment, June 2008, 577. https://doi.org/10.2147/NDT.S2749.
- Didden, Robert, Hubert Korzilius, Peter Sturmey, Giulio E. Lancioni, and Leopold M. G. Curfs. “Preference for Water-Related Items in Angelman Syndrome, Down Syndrome and Non-Specific Intellectual Disability.” Journal of Intellectual & Developmental Disability 33, no. 1 (March 2008): 59–64. https://doi.org/10.1080/13668250701872126.
- Holm, V. A., S. B. Cassidy, M. G. Butler, J. M. Hanchett, L. R. Greenswag, B. Y. Whitman, and F. Greenberg. “Prader-Willi Syndrome: Consensus Diagnostic Criteria.” Pediatrics 91, no. 2 (February 1993): 398–402.
- Laan, Laura A. E. M., and Alla A. Vein. “Angelman Syndrome: Is There a Characteristic EEG?” Brain & Development 27, no. 2 (March 2005): 80–87. https://doi.org/10.1016/j.braindev.2003.09.013.