Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here, we report two cases of episodic ataxia type 2 (EA2) in a 63-year-old woman and her 36-year-old daughter. The mother experienced recurrent attacks of cerebellar dysfunction lasting 4 to 5 hours since the age of 41 years. On several occasions, she was admitted to the emergency room, where she was diagnosed with epilepsy or stroke. Based on these diagnoses, she was treated with antiepileptic or anticoagulant drugs, but both treatments were eventually discontinued. The frequency of the attacks increased after the patient reached the age of 62. Interictal neurological examination demonstrated signs of slight cerebellar ataxia, i.e. saccadic eye movements, gaze-directed nystagmus, and mild truncal ataxia. Brain magnetic resonance imaging (MRI) showed cerebellar vermis atrophy. Electroencephalography (EEG) revealed various spike and wave patterns: solitary spikes, spike-and-slow wave complexes, and slow wave bursts. Photoparoxysmal response (PPR) type 3 was also observed. Treatment with acetazolamide abolished the patient's attacks almost completely. The daughter started experiencing 5- to 10-minute ataxic episodes at the age of 16 years. Based on her epileptiform EEG activities with PPR (type 2), antiepileptic drugs (valproate and zonisamide) were prescribed. Despite pharmacological treatment, the attacks recurred; however, their frequency gradually decreased with time, until they almost entirely disappeared when the patient was 33. Unfortunately, migraine-like headaches arose instead. Subtle truncal ataxia was observed during interictal periods. Sanger sequencing of the exons of the CACNA1A gene revealed a novel single base deletion (c.3575delA) in both patients. Despite the difference in age of onset and clinical course, both patients showed clearly epileptiform EEG activities without experiencing the concurrent epileptic episodes. Thus, EA2 is a disease that may be misdiagnosed as epilepsy or stroke in the field of emergency medicine.
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PMID:Episodic ataxia type 2 manifests as epileptiform electroencephalographic activity with no epileptic attacks in two family members. 2702 91

Autosomal-dominant episodic ataxias (EAs) represent a clinically and genetically heterogeneous group of disorders characterized by recurrent episodes of cerebellar ataxia (CA). Ataxia episodes are usually of short duration and often triggered by specific stimuli. There are currently seven classified subtypes of EA. EA types 1 and 2 have the highest prevalence and are therefore the clinically most relevant. Between attacks, EA 1 is associated with myokymia. In EA 2, often an interictal downbeat nystagmus with other cerebellar ocular dysfunctions is present; patients with EA 2 may display slowly progessive ataxia and vermian atrophy. EA 1 and 2 are both channelopathies, affecting the potassium channel gene, KCNA1, in EA 1 and the PQ calcium channel-encoding gene, CACNA1A, in EA 2. The types EA 3 to 7 are very rare and have to be further elucidated. Here, we review the historical, clinical, and genetic aspects of autosomal-dominant EAs and their current treatment, focusing on EA 1 and 2.
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PMID:The Clinical Spectrum of Autosomal-Dominant Episodic Ataxias. 3071 67

Episodic ataxia is a genetically heterogeneous neurological condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2, caused by calcium voltage-gated channel subunit alpha1 A (CACNA1A MIM: 601011) mutation, is the most common form of episodic ataxia. It is characterized by recurrent attacks of imbalance associated with interictal nystagmus lasting hours to days and triggered by emotional stress or exercise. In this article, we report a novel heterozygous intronic variant c.5743+14A>G in the CACNA1A gene in a Saudi family. To the best of our knowledge, this variant has not been described in the literature or reported in public mutation databases. This report indicated that acetazolamide is not beneficial, and it may be even harmful to patients with episodic ataxia type 2 if used in later stages. In addition, treatment with 4-aminopyridine did not show any efficacy to improve walking or balance in our patient, which indicates the importance of early initiation of therapy before the later stages of the disease. Further research is needed to explore potential treatments for this challenging disease.
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PMID:A novel mutation in CACNA1A gene in a Saudi female with episodic ataxia type 2 with no response to acetazolamide or 4-aminopyridine. 3088 62

Episodic ataxias (EAs) are characterized by recurrent, discrete episodes of vertigo and ataxia. EA1 and EA2 are the two most common forms. In the interictal interval, myokymia is typically present in EA1, whereas EA2 patients present with interictal nystagmus. Specific pharmacological therapies are available for EA1 and especially EA2. We briefly discuss the case of an Italian young man with EA2, with a novel de novo CACNA1A mutation, who in our opinion is particularly illustrative for introducing the therapeutic approach. Acetazolamide could fully suppress EA episodes in our patient. We also provide a perspective review of the topic. 4-Aminopyridine is another valid treatment option. For EA1 (and for rarer EAs), the therapeutic possibilities are more limited. Carbamazepine is probably the treatment of choice for EA1, but the optimal treatment plan is unknown. A better understanding of the molecular processes involved in the mediation of EAs will lead to more specific and efficacious therapies for this still elusive group of disorders.
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PMID:Therapy of episodic ataxias: case report and review of the literature. 3089 Oct 74

The genetic testing of hereditary ataxias includes screening for CAG-repeat expansions as well as pathogenic variants and nontranslated oligonucleotide expansion, which can cause spinocerebellar ataxia (SCA). Genotype-phenotype correlations of several SCA subtypes are difficult to establish, and the underlying mechanisms remain unclear. Here, we report a 58-year-old male patient who presented with severe generalized ataxia, horizontal gaze-evoked nystagmus, cognitive impairment and a positive family history of gait difficulties. Genetic panel diagnostics revealed a new nonsense pathogenic variant in the CACNA1A gene (c.2983G>T; p. Glu995*) that segregated with the phenotype in three clinically affected family members. This gene is related to SCA type 6 (SCA6), episodic ataxia type 2, familial hemiplegic migraine type 1, among others. When it is supported by the clinical findings and family history, additional DNA sequencing beyond fragment length analysis should be performed.
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PMID:New Nonsense Variant c.2983G>T; p.Glu995* in the CACNA1A Gene Causes Progressive Autosomal Dominant Ataxia. 3312 Dec 21


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