Rett and Rett-like syndromes [41 genes]

Epilepsy is a common neurological disorder whose prevalence is 5-8 in every 1000 individuals, with a cumulative lifetime incidence of 3%1. The underlying causes are multiple and heterogeneous. Some of these forms of epilepsy will have an identifiable genetic cause and more and more genes are known responsible for some of these forms of epilepsy, previously labeled as ‘idiopathic’.

The clinical manifestations of the different forms of epilepsy will provide very valuable information when deciding to request a genetic study since certain epileptic syndromes will guide the selection of the most appropriate study. To this end, we have designed an offer of panels that attempt to collect the most common causes of epilepsy from a genetic point of view, classified based on the epileptic phenotype to carry out a directed diagnostic genetic study and maintaining a panel general for more imprecise semiological classifications or more complex cases where it is necessary to cover a broad differential diagnosis

Rett syndrome is a rare genetic disease that causes problems in development and the nervous system, mostly in girls. It is related to autism spectrum disorder. At first, babies with Rett syndrome appear to grow and develop normally. However, between three months and three years, they stop their development and may even lose some skills. Symptoms include:

• Loss of speech
• Loss of hand movements, such as grasping things
• Compulsive movements such as hand wringing
• Balance problems
• Respiratory problems
• Behavioral problems
• Learning problems or intellectual disabilities

Traditionally, genetic studies in epilepsy have been relegated to complex or refractory patients. However, there are many cost-effective benefits to considering requesting a genetic test within the first tests in a patient who presents with a form of epilepsy. On the other hand, increasingly, studies in epilepsy do not only seek a diagnosis but also an approach to individualized medicine in which the finding of a variant in a certain gene can also provide very valuable help when selecting the best therapeutic strategy.

Clinical suspicion of Rett syndrome

Various studies carried out on the diagnostic performance of genetic panels for epilepsy place a diagnostic rate of around 15-25%. Of course, this performance varies depending on patient selection, clinical indication, age, and the presence of family history. It is likely that we still do not know many of the genes involved in epilepsy, although it is worth remembering that since it is such a common and heterogeneous disease, it is necessary to place it in its multifactorial context. Studies aimed at more selected patients have achieved diagnostic rates of up to 60-70% in early-onset epileptic encephalopathies, for example.