The etiology of cerebral palsy (CP) and intellectual disability (ID) is attributed to a wide variety of factors and the causal mechanism is unknown in most cases, especially in adults. The common belief is that the main cause is hypoxia (lack of oxygen) during childbirth. However, recent studies show that this would only explain 10% of cases and, in addition, sometimes there is an underlying genetic alteration that predisposes this brain ischemia to occur.
The scientific advances that have occurred in recent years have made it possible to reveal that a significant proportion of PC and DI are due to genetic alterations. When a state-of-the-art genetic study (exome) is performed in adults with CP or ID, we find pathogenic mutations in 10,5% of cerebral palsy and 66% of intellectual disability.
Currently, the pediatric diagnostic protocols in our environment already take into account the possibility of a genetic origin and targeted tests are performed when there is a suspicion. However, in many adults with PC, thediagnostic study which was carried out when they were at a pediatric age did not count on current scientific advances, so that it did not allow diagnosing many of the causes that can be detected today.
Benefits of diagnosis in adults with cerebral palsy
Although the usefulness of performing a comprehensive diagnostic study in cases of neurodevelopmental disorders in pediatric age is not questioned, when it comes to adults who spend their whole lives with the diagnosis of cerebral palsy, it is often not considered need to carry out this type of study because there is a false idea that it will not have a clinical repercussion for the person with CP. However, adults with cerebral palsy and their families may also benefit from obtaining an etiologic diagnosis:
- It allows them to access the appropriate resources and associations of affected patients.
- Studies show that 75% of patients and families want to know the cause of cerebral palsy or intellectual disability.
- Knowing the diagnosis allows monitor possible associated comorbidities. For example, there are syndromes that associate endocrinological problems or heart problems.
- In some cases they may exist specific treatments or risk of side effects with certain treatments. For example, there are epileptic encephalopathies for which certain drugs are contraindicated.
- It allows to explain the clinical evolution, the vital prognosis and the expectations regarding the treatment options. Many times we find that adults with CP have motor deterioration, parkinsonism or behavioral alterations that are typical of the natural evolution of a genetic syndrome. Being able to explain why this worsening is happening is therapeutic in itself.
- Genetic counseling When it is detected that the origin of CP is genetic, it is necessary to study whether it is due to a genetic alteration de novo (that is, it has appeared for the first time in the person with CP) or whether it is inherited from one of his parents . Thus, it is possible to know the risk that other family members may suffer from it or that they may pass it on to their children. With the genetic information, other relatives can consider the option of carrying out a pre-implantation genetic study.
- The possibility of participate in clinical trials that help find an effective treatment for their pathology. Although there are currently no human clinical trials to treat and cure the neurological sequelae of cerebral palsy, there are clinical trials with drugs that attempt to improve seizure control, spasticity, or behavioral disturbances.
Currently there are no clinical guidelines that indicate the protocol to follow for the etiological study of the cerebral palsy in adults, so the recommendation is to follow the indications of the pediatric guidelines. In these, the first step is to make one complete medical history, which includes all available data on pregnancy, birth, early development and family history. They are also valued associated comorbidities (epilepsy, autism spectrum disorder...) and one is carried out physical and neurological examination. They are also performed neuropsychological tests to assess whether there is any degree of intellectual disability.
The next step is to raise the complementary explorations that can help us: image tests (for example, cranial magnetic resonance imaging), electroencephalograms o metabolic studies. Finally, it comes up the genetic study, which can consist of different techniques such as the karyotype, CGH array or exome. If the genetic study is negative, but the suspicion of a genetic origin is high, the recommendation is to repeat it every 3-5 years, since new genetic alterations are constantly being discovered that can be the cause of the disease.
The etiological study of adult patients with cerebral palsy at the Aspace Catalunya Foundation
Approximately half of the patients we follow at the Aspace Catalunya Foundation are adults and in many of them the cause of their cerebral palsy is unknown. We try to carry out the protocols mentioned above with these people, along with a detailed medical history and performing them complementary explorations indicated If we consider it appropriate, we contact the corresponding reference centers so that genetic tests can be carried out.
An example of this diagnostic approach has made it possible to diagnose, in an adult patient with CP without a known cause, an encephalopathy associated with a mutation in the CHD2 gene. By knowing the mutated gene, we were able to understand many of the symptoms the patient presented and we were able to treat epilepsy in a more personalized way and explain to relatives the reason why he is presenting with a worsening of his gait and behavior and the reason why he is presenting with photosensitive crises.
We believe that an accurate diagnosis can benefit all our patients/families, whether children or adults.
Bibliographic references
1. Moreno-De-Luca A., Millan F. et al Molecular Diagnostic Yield of Exome Sequencing in Patients with cerebral palsy JAMA. 2021;325(5):467-475.
2. Frueh JS, Press DZ, Sanders JS. Diagnosis and Workup of Intellectual Disability in Adults: Suggested Strategies for the Adult Neurologist. Neurol Clin Pract. 2021 Dec;11(6):534-540
3. Aravamuthan BR, Shusterman M, Green Snyder L, Lemmon ME, Bain JM, Gross P; For Simons Searchlight; Cerebral Palsy Research Network. Diagnostic preferences include discussion of etiology for adults with cerebral palsy and their caregivers. Dev Med Child Neurol. 2022 Jun;64(6):723-733. doi: 10.1111/dmcn.15164. Epub 2022 Jan 29.
4. Beltrán-Corbellini Á, Aledo-Serrano Á, Møller RS, Pérez-Palma E, García-Morales I, Toledano R and Gil-Nagel A (2022) Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies. front Neurol. 13:777115
