This website provides information on patients with variants in the KCNMA1 gene, including clinical data, molecular data, management and research options.
The KCNMA1 linked channelopathy is a heterogeneous multisystem disorder associated with variants in the KCNMA1 gene. This disorder was first identified in 2005 and is classified as an extremely rare disease, with only 103 individuals identified as of 2022. The syndrome is characterized by overlapping seizure/epilepsy disorder, movement disorder phenotypes, developmental delay, intellectual disability, and in some cases by brain and skeletal malformations. The most common symptomatic findings associated with KCNMA1-linked channelopathy are episodic dyskinesia and epilepsy. EEG workups are required to delineate between seizures/epilepsy and the movement disorder. As more patient data is collected, the prevalence of neurodevelopmental abnormalities including autism spectrum disorder, developmental delay and intellectual disability is being evaluated. Some patients exhibit structural brain abnormalities including variable white matter and cerebellar atrophy.
Not all individuals with a mutation in the KCNMA1 gene will have these features. Furthermore, it is not yet understood whether all variants obtained in patients are causative for the observed symptoms, or if other genetic and environmental factors contribute. The strongest association between a specific type of patient variant and certain symptoms is the association of paroxysmal non-kinesigenic dyskinesia type 3 (PNKD3) and ‘gain-of-function’ variants. However, other variants also can present with PNKD, necessitating caution when interpreting such associations from such a small patient population with differences in symptomatic presentations.
This website was created to collect and share and collect information for better diagnosis, treatment, and support for patients with genetic findings associated with the KCNMA1 gene.
Andrea Meredith, PhD, Professor, University of Maryland School of Medicine, Baltimore, USA, ameredith@som.umaryland.edu