Offering hope to Amish families affected by genetic disorders

Working closely with the community and their clinical care providers, the project highlights the immense clinical, social and scientific value of undertaking translational research into the causes of genetic disorders within a community setting. This approach ensures that patients, families and the wider community benefit directly and in real time from the work taking place in their community.

Each and every one of us carries alterations in our genetic code that have the potential to give rise to genetic disease, and our ancestry plays an important role in determining which genetic disorders we may be more or less at risk of inheriting. The founders of the Amish community originated in Europe and travelled to the USA. The genetic alterations that they carried with them to the USA were passed on to subsequent generations, whereas those that they did not carry could not be passed on. This means that over time some genetic disorders have become more common within the community, whereas others are not present in the community at all.

Thanks to funding from the Medical Research Foundation’s Fleming Memorial Fund for Medical Research, Dr Emma Baple and Professor Andrew Crosby from Exeter have communicated their findings beyond the scientific press to groups of people most likely to benefit from their discoveries – including information days for families, educational meetings for health care workers and educational providers.

Before the project began in 2000, less than five per cent of Amish individuals with a genetic disorder from communities in which they work had been given a much-needed diagnosis. Due to the efforts of the research team from Exeter, their clinical co-workers, academic collaborators and the Amish community, the current figure is now closer to 70-80 per cent. This work has dramatically reduced the health, social and financial burden of inherited genetic disorders on the community.

Professor Andrew Crosby said: “Findings from our project have profoundly improved knowledge of genetic disorders and in turn revolutionised the approach to molecular diagnostic testing and genetic counselling in these communities. There are immediate benefits, in that health care providers can now offer very specific diagnoses of particular genetic disorders, often at a much earlier stage. In turn, that means families are able to receive accurate counselling and information about disease progression and prognosis.”

Dr Emma Baple added: “For many of the families we have worked with, the specific genetic cause of the disorder affecting them was not known to medical science prior to our research studies. Obtaining a diagnosis was very important for these families. Similarly, the knowledge learned from these studies was important for aiding diagnoses for other families worldwide affected by these conditions. Many Amish children and adults affected by genetic disorders often undergo multiple expensive investigations in search of a diagnosis. Our work now means that clinicians are able to offer a rapid, inexpensive diagnostic genetic test that often can prevent the need for these other tests.”

The Windows of Hope team works closely with the New Leaf Clinic for Special Children in Ohio, and other regional specialist clinics including the Center for Special Children in La Farge, Wisconsin. Dr Olivia Wenger, Paediatrician and Medical Director at the New Leaf Clinic for Special Children, said: “Research helps us to be much more effective in gathering information that’s pertinent to the population we serve. I can quickly focus the tests that I order when I’m seeing a child with an unknown cause of developmental delay because of the work that’s done through the research group in Exeter. They’ve described multiple conditions that are common in our community that I wasn’t aware of before I started practice here seven years ago. They work hard to make sure that I’m aware of them and that other people who serve this community are also aware of them, and that we have the resources we need to expedite early diagnosis. It is the best example of translational work that I have seen in my 15 years of practice.”

On the importance of local meetings for families to discuss these findings with researchers and health professionals, Dr Wenger added: “The meetings are low-key and comfortable. I think it’s a wonderful way to remind the families that we’re all in this together.”

Malinda Yoder, mother to two children affected by a genetic disorder, Sara Mae and Kyle, said: “The research team did a great job explaining everything to us on our level of understanding. After a few years we were told they had found the gene that was probably causing these symptoms. It was not a condition that had been given a name or studied, so it didn’t have a name, but at least we knew that much. Previously people would ask what condition our children had, we would just kind of explain some of the symptoms and didn’t really have an answer. To know was really helpful because we knew they actually had a genetic disorder.”

One example of the project’s benefits to the community relates to children with a genetic disorder that affects their development, who have previously undergone many expensive, and sometimes invasive and painful clinical tests, in order to reach a diagnosis. The team discovered that a common clinical feature was an unusually long big toe, meaning a diagnosis can be made simply by removing the child’s socks.

Other examples entails other conditions in which Amish children have previously been given a diagnosis of ‘autism’. The Exeter (@RDExeter) group was able to define the specific genetic cause and clinical features of these conditions, which enabled the team to develop cost effective genetic diagnostic testing to be provided alongside providing families a much needed name for each condition. Additionally, knowledge of the specific clinical course of each condition enabled accurate prognostic information and clinical management strategies to be implemented, including for the development of seizures and other neurological complications of these conditions.

The project website (www.WOHproject.com) was developed with support from the Medical Research Foundation and houses a searchable database of all known inherited disorders affecting the community. This resource is widely used by clinicians, genetic counsellors, healthcare workers, teachers and academics worldwide, providing a crucial source of information for both families impacted by these conditions, as well as healthcare and educational teams, to aid management of these disorders.

The Foundation’s support has also enabled the University of Exeter team to launch a Massive Open Online Course (MOOC), provided through FutureLearn, to teach academics and clinicians about the extraordinary translational benefits of a community approach to genomic medicine and research. The course includes video and audio recordings of Amish families describing their journey in search for a diagnosis and how the research undertaken by the Windows of Hope team has helped them and other families like them.