
Advances in Pitt-Hopkins syndrome research

Pitt-Hopkins syndrome is a rare genetic disorder caused by mutations in the TCF4 gene, which plays a key role in the normal development of the nervous system. Children with this condition often experience developmental delays, severe intellectual disabilities, and communication difficulties. A similar situation occurs in Rett syndrome, but the mutations are found in the MECP2 gene.
One of the main challenges in researching these types of syndromes is the search for biomarkers to assess the effectiveness of treatments and clinical trials. This means identifying specific molecules that provide information about how well treatments are working. In this regard, Judith Armstrong's team has conducted a multi-omic analysis (a full study of RNA, DNA, and proteins of the cell) of fibroblasts from Rett syndrome patients with an MECP2 mutation to understand the molecular consequences of this mutation.
Armstrong explains that the next step is to confirm these findings in brain cells from Rett syndrome patients and see if these biomarkers can also be detected in blood, as it is a more easily accessible tissue. This could speed up the diagnosis and monitoring of the disease.
They also plan to conduct these studies on samples from 10 patients with Pitt-Hopkins syndrome. Due to the very low prevalence of this disorder, a sample of 10 patients is large enough to yield meaningful results. Armstrong makes a call for support:
"In rare diseases like Pitt-Hopkins syndrome, having a sample of 10 patients is very challenging, which is why we need the collaboration and involvement of all affected families. This sample bank of 10 Pitt-Hopkins patients will be one of the largest in the world for this syndrome. We are immensely grateful to the families."
These studies will help introduce new technologies and diagnostic tools to improve the care of patients with neurodevelopmental disorders, enhancing their well-being. Additionally, in the longer term, gaining a detailed understanding of the altered pathways and the disease's pathophysiology will allow for the development of more targeted and successful drug therapies.
*Source: Research in Pitt-Hopkins at Sant Joan de Déu, a neurodevelopmental disorder