Progressive myoclonic epilepsy is a neurodegenerative disorder characterized by myoclonic seizures and variable neurologic symptoms, including cognitive decline and persistent movement abnormalities (Bird and Shaw, 1978).
For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, ... Progressive myoclonic epilepsy is a neurodegenerative disorder characterized by myoclonic seizures and variable neurologic symptoms, including cognitive decline and persistent movement abnormalities (Bird and Shaw, 1978). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Bird and Shaw (1978) reported a girl with juvenile-onset progressive myoclonic epilepsy. At age 15 years, she developed an awkward gait, clumsy hand coordination, deteriorating cognition, and nocturnal seizures associated with irregular EEG findings. The disorder was progressive, ... Bird and Shaw (1978) reported a girl with juvenile-onset progressive myoclonic epilepsy. At age 15 years, she developed an awkward gait, clumsy hand coordination, deteriorating cognition, and nocturnal seizures associated with irregular EEG findings. The disorder was progressive, and she later developed nystagmus, dysarthria, ataxia, fine tremor, loss of distal vibratory sense and reflexes, and pes cavus. Late in the disorder, she developed severe myoclonic jerks and visual impairment, and became bedridden. She died of pneumonia at age 19 years. Neuropathologic examination showed brain atrophy and multifocal lesions in the cerebral cortex characterized by hypertrophic astrocytes, spongy degeneration, and neuronal loss. Fibrillar rod-like structures were seen in the hippocampus. There was widespread loss of Purkinje cells in the cerebellum, neuronal loss and gliosis in the brainstem, including the substantia nigra, and degeneration of the dorsal column of the spinal cord. Family history revealed a younger brother with a similar, but milder, disorder with onset at age 14. He had tremor, mild pes cavus, nystagmus, and peripheral neuropathy. At age 17, he did not have cognitive decline or myoclonic seizures, but he did have EEG abnormalities. Bird and Shaw (1978) noted some phenotypic similarities to the Ramsay-Hunt syndrome (159700) and dentatorubral degeneration (DRPLA; 125370).
In the 2 sibs with progressive myoclonic epilepsy originally reported by Bird and Shaw (1978), Tao et al. (2011) identified a heterozygous mutation in the PRICKLE2 gene (608501.0001). An unrelated patient with myoclonic seizures was heterozygous for a ... In the 2 sibs with progressive myoclonic epilepsy originally reported by Bird and Shaw (1978), Tao et al. (2011) identified a heterozygous mutation in the PRICKLE2 gene (608501.0001). An unrelated patient with myoclonic seizures was heterozygous for a different PRICKLE2 mutation (608501.0002); no further details on this patient were provided. Tao et al. (2011) also identified 2 different heterozygous mutations in the PRICKLE1 gene (R144H; 608500.0002 and Y472H; 608500.0003, respectively) in 2 unrelated patients with variable severity of myoclonic epilepsy (EPM1B; 612437). Tao et al. (2011) concluded that PRICKLE signaling is important in seizure prevention, and presented 2 hypotheses: (1) that PRICKLE affects cell polarity and contributes to the development of a functional neural network and (2) that PRICKLE affects calcium signaling, which may play a role in seizure genesis if disrupted.