Brachydactyly, cutis laxa, craniosynostosis, Marfan syndrome – few people have ever heard of these rare diseases. Even the best-trained paediatricians are often unable to recognize a rare disease. The parents of children with such diseases often go from one doctor to the next, only to be met with a mystified shrug of the shoulders. Providing a rapid diagnosis in such cases is impossible. In addition, most rare diseases are not included in the accounting systems of the health insurance companies, and the treatment options are very limited. Moreover, the affected patients and their families can expect little or no help from the industry – the corresponding patient groups and drug markets are simply too small.
Stefan Mundlos, Research Group Leader at the Max Planck Institute for Molecular Genetics investigates the causes of rare diseases with his team: he is specialized in the genomic analysis of rare bone diseases. Using the very latest genome analysis technology available at the Berlin-based Institute, they look for the genes responsible for skeletal disorders and analyze their function. The knowledge they gain can be used as a basis for further research on new treatment options.
Thanks to the generous support of the Kindness for Kids Foundation, it has been possible to complete the crucial initial steps towards attaining this objective. The research centres on the genomic analysis of malformations of the extremities in Ondine Syndrome - a rare congenital disease of the central nervous system that is associated with disordered respiratory regulation - and of quadrupedal locomotion, a neurological disorder which results in patients only being able to walk on their hands and feet.
Ideally, the results of Mundlos’ scientific projects filter down to medical practice – once his team has succeeded in identifying the cause of a previously mysterious rare disease and enabling its diagnosis using a new genetic test. Every day, the doctors encounter rare clinical pictures that present similarities and differences in terms of their characteristics and symptoms, and every day they receive blood samples and files from patients all over the world. They have now assembled a collection of diseases that they are recording systematically. This enables the extrapolation of certain "phenotypes", as the geneticists call them, from all of the described disease patterns.
The Research Group works closely with the Institute for Medical and Human Genetics (IMG) at the Charité university hospital in Berlin and with the Berlin-Brandenburg Center for Regenerative Medicine (BCRT). The scientists feed the constantly growing information on rare diseases into a computer programme. The software links different symptoms and eventually assigns them to similar cases that have been encountered by colleagues in other places. It can also create cross references and stores data about the underlying genetic mutations and molecular mechanisms. The software’s intelligence grows with the volume data, and this enables the doctors to make increasingly accurate diagnoses. Thus, the basis is being established here for an approach to rare disease diagnostics that is in tune with the digital possibilities of the 21st century.
"Knowing about the cause of a disease is a relief for the parents involved," says Stefan Mundlos. During consultations at the Charité, he is often confronted with the pressing question as to whether another child or a grandchild could be affected by the same illness. And if the answer is yes, what is the probability that it will happen. "A correct diagnosis is crucial," explains the paediatrician, "Without a diagnosis there can be no prognosis and a treatment cannot be developed." The problem: due to the fact that the research has only been very recently initiated, diagnoses are still lacking for many rare diseases, as corresponding genetic tests are still not available.
Image: MPI for Evolutionary Anthropology