Angelman Syndrome Deletion Size: Does It Matter?

• One study looked at data from the North American natural history study (NHS), which includes several developmental assessments. Individuals living with Class 1 deletions had lower average scores, but those differences were not statistically significant on 18 out of 19 assessments. The Clinical Severity Scale (an assessment completed by a physician) was the one assessment where deletion size significantly impacted the scores, with individuals living with Class 2 deletions having better scores than those living with Class 1 deletions. The authors concluded that any differences between deletion classes are small from a practical perspective.  It is possible that a larger study with more participants may be able to identify additional differences (Keute et al, 2021). 

• An analysis specifically of the Bayley assessment in individuals living with AS who participated in the NHS found no significant differences between Class 1 and Class 2 deletions in the developmental profiles and how development progressed (Sadhwani et al, 2023).     

• Another study using data from participants in the NHS looked at reaching developmental milestones and daily living skills.  Overall, the study found significant variability in how likely it was that an individual might achieve a skill, and that variability was seen within a genotype and deletion Class.  For example, learning to do daily living skills like feeding oneself had a very broad range of ages, even within a genotype or deletion class. This study also found no differences in development for Class 1 and Class 2 deletions in most developmental skills (Sadhwani et al, 2024).   

• Data from the early NHS showed no statistically significant differences in developmental scores between Class 1 and Class 2 deletions (Tan et al, 2011).   

• Another study of about 40 individuals living with deletion AS found that Class 1 and 2 deletions had similar scores on tests of cognition and adaptive behavior.  However, participants in this study who had Class 1 deletions had greater impairment in social affect (expressing and interpreting emotions), repetitive behaviors, and sensory aversions, consistent with more autism spectrum symptoms.  Participants in this study were retested a year later, and these differences were still present (Peters et al, 2012).  

• An older study of about 40 individuals living with deletion AS found that individuals living with Class 2 deletions learned to sit without support at a younger age and were able to make more vocalizations, as compared to individuals living with a Class 1 deletion.  There were no other statistically significant differences in development (Varela et al, 2004).    

• A small study of 16 individuals living with Deletion AS found that individuals with Class 1 deletion had more daily seizures, more febrile seizures, more debilitating seizures, and needed more therapies than individuals with a Class 2 deletion (Valente et al, 2013). 

Codes for a piece of the GABA-A receptor. The GABA-A receptor helps regulate brain activity by interacting with GABA, the brain’s main inhibitory neurotransmitter.  "Inhibitory" means it helps calm down overactive nerve signals, preventing the brain from becoming overstimulated.  GABA-A receptors are involved in regulating many brain functions including anxiety, sleep, learning, and memory.  

Codes for a piece of the GABA-A receptor. The GABA-A receptor helps regulate brain activity by interacting with GABA, the brain’s main inhibitory neurotransmitter.  "Inhibitory" means it helps calm down overactive nerve signals, preventing the brain from becoming overstimulated.  GABA-A receptors are involved in regulating many brain functions including anxiety, sleep, learning, and memory. 

Codes for a piece of the GABA-A receptor. The GABA-A receptor helps regulate brain activity by interacting with GABA, the brain’s main inhibitory neurotransmitter.  "Inhibitory" means it helps calm down overactive nerve signals, preventing the brain from becoming overstimulated.  GABA-A receptors are involved in regulating many brain functions including anxiety, sleep, learning, and memory. 

Codes for the P protein, which is needed for skin, hair, and eye pigmentation. P protein is found in the melanin-producing cells and is likely involved in the production of melanin, the pigment responsible for coloring skin, hair, and eyes.  Missing one copy of OCA2 may result in lighter hair and skin than other family members, which is seen in many individuals living with Deletion AS.  If an individual makes no P protein at all (because they have genetic variants on BOTH copies of the OCA2 gene—this is not typically the case in AS), the individual will have oculocutaneous albinism.  Oculocutaneous albinism causes significantly reduced pigment in the hair, skin, and eyes, as well as vision problems.    

Codes for a magnesium transporter that helps maintain proper magnesium concentrations in the brain.   

Codes for a selective magnesium transporter (only one type of magnesium) that helps maintain proper magnesium concentrations in the brain.    

Codes for a protein important in organization and structure in brain cells, including the development of synapses (connections between neurons) and white matter in the brain.  

Codes for a protein that helps the formation of microtubules (scaffolding within the cells), which is needed for moving around proteins and for cells to divide properly to make new cells.