PRRT2-related disorders encompass a spectrum of neurological conditions primarily associated with movement abnormalities and seizure activity. The most notable disorders linked to PRRT2 are BFIS and PKD but also hemiplegic migraine and more severe epilepsy phenotypes such as developmental epileptic encephalopathies are described. BFIS manifests with multiple seizure types in normally developing infants, beginning at a mean age of 6 months and usually remitting before the age of 2 years. PKD is characterized by episodes of unvoluntary movements lasting for seconds to minutes mainly induced by fast voluntary movements. In the initial phase, up to 100 episodes per day can appear. During an episode, individuals may experience a variety of involuntary movements, including dystonic postures (abnormal muscle contractions leading to twisted positions), chorea (irregular, rapid movements), and athetosis (slow, writhing movements). These can affect different parts of the body, including limbs and facial muscles.
Symptoms often begin in childhood or adolescence, typically between ages 5 and 15 years; however, there is considerable variability in age at onset among individuals. There is significant heterogeneity in symptom presentation among affected individuals—some may experience frequent episodes while others have infrequent occurrences; this variability complicates diagnosis and management.
Most individuals with PRRT2-related disorders have normal cognitive function throughout their lives. However, some case reports suggest a potential association with mild cognitive impairment or learning difficulties in certain patients. Given the autosomal dominant inheritance pattern associated with PRRT2 mutations, there is often a family history of similar movement disorders or epilepsy within affected families.
PRRT2