Session workshops
At this point, the scientific participants could decide on their preferred area of focus, with split sessions offering the latest knowledge on genetic testing, and another on the related subject of family screening.
Genetic testing and variants in angioedema
The first presentation in this workshop was given by Dr Matija Rijavec from the University Clinic of Respiratory and Allergic Diseases in Slovenia. He presented the concept of ‘variant curation’, in which clinicians interpret the findings of genetic tests to establish clinically relevant and harmful variations in genes, and that genetic sequencing alone is not sufficient. He concluded that variant curation could improve diagnostic accuracy and make family resting more reliable. This was especially important in more genetically diverse forms of HAE.
The next topic for discussion, Managing incidental findings in HAE with normal C1 inhibitor-related genes, was led by Professor Anastasios Germenis from the University of Thessaly in Greece. He suggested to the audience that for every diagnostic success, there are around two patients for whom a genetic testing report leads to more questions than answers. There are two key questions when an unexpected result arises during the genetic analysis:
- Should the genetic lab report such results back to the ordering clinician?
In answering this question, Prof Germenis said that it is not justifiable to report unsolicited findings unless more reliable estimates of the importance and impact are available.
- What should the clinician do once they are informed?
Here, he presented a decision tree outlining actions based on the various genetic findings. The next steps included gathering further medical history from patients and their families, and submitting potentially novel genetic mutations to registries.
The final presentation in this workshop, Genetic determinants in HAE with normal C1 inhibitor, was given by Dr Agnes Szilágyi from the Semmelweis University in Hungary. She focused on the experiences from the Hungarian ACARE center around the known genes responsible for HAE with normal C1 inhibitor. She suggested that, although the rate of positive samples is low, the risk of a fatal attack is high, so screening for known variants is recommended.
Family screening
In the workshop focused on family screening, Oscar Calderón Llosa from SANNA Clínica el Golf in Perú presented a series of cases in which genetic screening led to an appropriate diagnosis of HAE, especially HAE with normal C1 inhibitor due to an FXII mutation. Through subsequent family screening, two more patients were identified, diagnosed, and treated, with further asymptomatic and symptomatic cases seen in the wider family.
The next speaker, Dr Isabelle Boccon-Gibod, from Grenoble Alpes University Hospital in France, focused on clinical cases and family screening in HAE. She presented a French family with HAE, starting from the index case of a woman diagnosed with HAE due to a SERPING1 pathogenic variant. She asked the audience to consider what they would do faced with the case study she described, including explaining the risk of transmission and the need to screen children as soon as possible. She suggested that testing asymptomatic family members is extremely important, and provided the following take-home messages:
- Genetic counseling is an essential component of HAE management
- It provides clear information on inheritance and familial risk
- Informing relatives is mandatory due to the potential severity of attacks
- Screening applies to all, including minors
- Children should be screened very early
- Early diagnosis improves safety, access to emergency treatment, and ultimately, the quality of care
Industry session: Intellia
The final industry-supported session was presented by Prof Danny Cohn from Amsterdam UMC in the Netherlands. He provided a background on the concept of gene editing therapy and its application in HAE. He then turned to the potential new gene editing therapy for HAE, called lonvo-z. He indicated that this works by altering the genetic information of specific liver cells so that they are permanently unable to produce plasma kallikrein. He concluded by showing that, beyond HAE, more than 100 clinical trials are currently investigating the use of CRISPR/Cas9 gene editing technology to treat diseases such as type-1 diabetes, sickle cell disease, and some forms of cancer.
