From the Guidelines
The prevalence of seizures in patients with CHD2 mutations is approximately 80-90%, with seizures often beginning in early childhood and including multiple seizure types. This is based on the understanding that CHD2 mutations cause a neurodevelopmental disorder characterized by epilepsy, developmental delay, and intellectual disability 1. The seizures typically begin in early childhood, often before 3 years of age, and can include multiple seizure types such as myoclonic, absence, generalized tonic-clonic, and atonic seizures. Some patients may develop Lennox-Gastaut syndrome or other epileptic encephalopathies. Key characteristics of CHD2-related disorders include:
- High prevalence of seizures due to the gene's critical role in brain development and neuronal function
- Regulation of chromatin remodeling and gene expression in the central nervous system
- Difficulty in controlling seizures, often requiring multiple medications or alternative approaches
- Treatment typically involves anti-seizure medications, though alternative approaches such as ketogenic diet or vagus nerve stimulation may be necessary in some cases. It's worth noting that while the provided study 1 focuses on paroxysmal kinesigenic dyskinesia and does not directly address CHD2 mutations, the general understanding of CHD2's role in neurodevelopmental disorders informs the high prevalence of seizures in affected patients.
From the Research
Prevalence of Seizures in Patients with CHD2 Mutations
- The prevalence of seizures in patients with CHD2 mutations is high, with all patients in the studied populations experiencing seizures 2, 3, 4, 5, 6.
- The age at seizure onset ranges from 3 months to 10 years, with a median age of 4 years 2 and a mean age of 26 months 3.
- Various types of seizures are observed, including generalized tonic-clonic, myoclonic, atonic, atypical absence, myoclonic-atonic, and spasm seizures 2, 3, 4.
- Multiple types of seizures are common, with 10 out of 17 patients in one study experiencing multiple types of seizures 2.
- Developmental disability and intellectual disability are common comorbidities, with 14 out of 17 patients in one study having developmental disability and 5 out of 17 patients having autism features 2.
- Seizures are often resistant to treatment, with 2 out of 17 patients in one study having refractory epilepsy 2.
Types of Seizures
- Myoclonic seizures are a common type of seizure, occurring in all 10 cases in one study 3.
- Generalized tonic-clonic seizures occur in 9 out of 10 cases, with a mean onset of 5.8 years 3.
- Atonic and myoclonic-atonic seizures also occur, with 40% and 30% of patients experiencing these types of seizures, respectively 3.
- Photosensitivity epilepsy is a distinctive feature of CHD2-related epilepsy, with 7 out of 10 patients in one study exhibiting exquisite clinical photosensitivity 3.
Genetic Characteristics
- De novo mutations of CHD2 are common, with 16 out of 17 patients in one study having de novo mutations 2.
- Novel mutations are frequently identified, with 11 out of 16 mutations in one study being novel 2.
- A hotspot mutation, Q1392TfsX17, may be associated with CHD2-related epilepsy 4.
- Mutations near the C-terminus of the CHD2 protein are significantly clustered, suggesting a potential functional importance of this region 6.