IllnessAtaxia, episodic; differential diagnosis

NGS +

Episodic ataxia refers to a group of related disorders that result in recurrent episodes of incoordination and ataxia. During these episodes, many patients also suffer from dizziness, nausea/vomiting, migraines, blurred or double vision, slurred speech and tinnitus. Seizures and hemiplegia may also occur during the episodes. In addition, some patients experience myokymia during or between seizures, with muscle spasms, stiffness and continuous fine muscle twitching/spasms under the skin. Ataxia episodes and the other symptoms can occur from early childhood into adulthood. They can be triggered by emotional stress, caffeine, alcohol, certain medications, physical activity and illness. The frequency of episodes ranges from several per episode to 1-2/year. Between episodes, some sufferers continue to experience ataxia, which can worsen over time, as well as additional nystagmus. There are at least 7 types of episodic ataxia, distinguished by symptoms, age of onset, duration of attacks and, if known, their genetic basis. Episodic ataxia can be caused by mutations in several genes, e.g. KCNA1, CACNA1A and CACNB4 as channel disorders relating to episodic ataxia types 1, 2 and 5, respectively. Mutations in the SLC1A3 gene are the cause of episodic ataxia type 6, a neurotransmitter disorder. In these 4 types, certain neurons become overexcited and disrupt normal communication between cells. The genetics for some of the other forms of episodic ataxia have not yet been worked out. Episodic ataxia is inherited in an autosomal dominant manner. As the molecular genetic yield rarely exceeds 60% of cases, a negative DNA test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK25442/

https://www.ncbi.nlm.nih.gov/books/NBK1388/

https://www.ncbi.nlm.nih.gov/books/NBK1138/

https://www.ncbi.nlm.nih.gov/books/NBK475803/

• Alias: Hereditary episodic ataxia
• Allelic: Alternating hemiplegia of childhood 2; Dystonia-12 (ATP1A3)
• Allelic: Catastrophic epilepsy, unusual apnea spells + postnatal microcephaly (ATP1A3)
• Allelic: Rapid-onset dystonia-parkinsonism (ATP1A3)
• Acetazolamide-responsive hereditary paroxysmal cerebellar ataxia (CACNA1A)
• Allelic: Convulsions, familial infantile, with paroxysmal choreoathetosis (PRRT2)
• Allelic: Developmental + epileptic encephalopathy 11 (SCN2A)
• Allelic: Myasthenic syndrome, congenital, 25 (VAMP1)
• Allelic: Seizures, benign familial infantile, 2 (PRRT2)
• Allelic: Seizures, benign familial infantile, 3 (SCN2A)
• CACNA1A-related episodic ataxia type 2 (CACNA1A)
• Cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss, CAPOS (ATP1A3)
• Epilepsy, juvenile myoclonic, 6 (CACNB4)
• Episodic ataxia [panelapp] (UBR4)
• Episodic ataxia, nystagmus-associated (CACNA1A)
• Episodic ataxia, type 1 (KCNA1)
• Episodic ataxia, type 2, EA2 (CACNA1A)
• Episodic ataxia, type 5 (CACNB4)
• Episodic ataxia, type 6 (SLC1A3)
• Episodic ataxia, type 9 (SCN2A)
• Episodic ataxia-8 [OMIM preliminary designation] (UBR4)
• Episodic ataxia/myokymia syndrome (KCNA1)
• Episodic kinesigenic dyskinesia 1 (PRRT2)
• Hypomagnesemia, AD (KCNA1)
• Migraine familial hemiplegic 1 (CACNA1A)
• Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Myokymia with periodic ataxia (KCNA1)
• Paroxysmal nonkinesigenic dyskinesia 1 (PNKD)
• Spastic ataxia 1, AD (VAMP1)
• Spinocerebellar ataxia 6 (CACNA1A)
• Susceptibility to epilepsy, idiopathic generalized, 9 (CACNB4)