Genetics of AS 102: Genotypes & Family Planning

Quick Overview

The session on the genetics of Angelman Syndrome (AS) aimed to enhance understanding of the condition’s variability, discuss genetic testing for family planning, and encourage confidence in navigating local resources. Speakers Katie Garbarini, a genetic counsellor, and Liz Jalazo, a clinical geneticist and mother of a child with AS, highlighted the genetic subtypes of AS, including deletions, mutations, imprinting centre defects, and paternal uniparental disomy. They emphasised the importance of recognising the diverse symptoms and challenges associated with each subtype, such as movement difficulties, communication issues, and behavioural challenges. The session encouraged participants to reflect on their experiences and share insights, fostering a supportive community. Additionally, the speakers addressed family planning considerations, noting that AS is typically non-inherited, but certain genetic circumstances can increase recurrence risk. They advised consulting genetic counsellors for personalised guidance.

The 2024 ASF Family Conference featured an insightful session on the genetics of Angelman Syndrome (AS), led by Katie Garbarini, a genetic counsellor and director of the LADDER Learning Network, and Liz Jalazo, a clinical geneticist and medical director for the Angelman Syndrome Foundation. The session aimed to deepen understanding of the variability within Angelman Syndrome, discuss genetic testing considerations for family planning, and encourage confidence in navigating local resources.

Understanding Angelman Syndrome Variability

Angelman Syndrome is often misunderstood as a singular condition, but it actually presents significant variability both genetically and symptomatically. The session began with a reflection activity, encouraging participants to consider the genetic subtype of their loved one with AS and the impact of various symptoms. This exercise highlighted the diverse experiences within the AS community.

Genetic Subtypes of Angelman Syndrome

Angelman Syndrome is caused by absent or reduced function of the maternal UBE3A gene, which is crucial for brain and spinal cord function. The session reviewed the genetic subtypes of AS, which include:

• Deletion: The most common subtype, involving the loss of multiple genes on the maternal chromosome 15.
• Mutation: A misspelling in the maternal UBE3A gene, leading to reduced function.
• Imprinting Centre Defects: Errors causing silencing of the maternal gene.
• Paternal Uniparental Disomy (UPD): Two copies of chromosome 15 from the father, with no maternal contribution.

The speakers also discussed mosaicism, where individuals have a mix of normal and affected cells, often resulting in milder symptoms.

Symptom Variability and Management

The session delved into the common symptoms of Angelman Syndrome, such as movement and balance difficulties, characteristic behaviours, learning challenges, and profound limitations in speech. Liz Jalazo shared personal insights from her experience as a parent of a child with AS, emphasising the importance of high expectations and tailored interventions.

Behavioural and Developmental Insights

Participants shared their experiences, revealing both commonalities and unique challenges. For instance, some children with AS exhibit advanced problem-solving skills despite communication barriers, while others face significant behavioural challenges linked to frustration and anxiety. The session underscored the importance of early intervention and consistent therapy to support development.

Family Planning and Genetic Testing

Katie Garbarini addressed the genetic aspects of family planning for those with a history of Angelman Syndrome. While AS typically does not run in families, there are rare inherited cases. Genetic counselling can provide valuable insights into recurrence risks and prenatal testing options.

Genetic Testing Options

The session highlighted various genetic testing methods, including:

• Amniocentesis and CVS: Diagnostic tests during pregnancy.
• Non-Invasive Prenatal Testing (NIPT): A maternal blood test that screens for certain conditions, though less accurate for AS.

Participants were encouraged to consult with genetic counsellors to explore these options and understand the implications for family planning.

Conclusion

The session concluded with an open invitation for questions and further discussion, emphasising the importance of community support and resource sharing. The speakers encouraged attendees to connect with local resources and continue learning about the evolving landscape of Angelman Syndrome research and care.

This session at the ASF Family Conference provided a comprehensive overview of the genetic and symptomatic diversity of Angelman Syndrome, offering valuable insights for families navigating this complex condition.