Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042571 (vertigo)
 7,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Episodic ataxia (EA) is a rare, disabling condition of autosomal dominant inheritance, but it is not a distinct clinical entity. Synonyms are familial periodic ataxia or hereditary paroxysmal cerebellar ataxia. Family members have a similar clinical syndrome; however, the syndrome varies considerably from family to family. At least two groups of disorders have been separated clinically: (1) episodic ataxia type 1 (EA-1), which manifests without vertigo and is associated with 'interictal' myokymia, and (2) episodic ataxia type 2 (EA-2), which often manifests with vertigo and is associated with 'interictal' nystagmus. EA-1 and EA-2 have been identified as channelopathies. EA-1 is due to different heterozygous missense point mutations in a voltage-gated (delayed rectifier) potassium channel gene (KCNA1/Kv1.1) on chromosome 12p13, whereas EA-2 is caused by mutations of the cerebral P/Q-type calcium channel alpha 1 subunit gene CACNL1A4 localized on chromosome 19p, which is highly expressed in the cerebellum. The diagnosis of EA-1 and EA-2 is important, since they can be easily treated and are often mislabeled. As effective as acetazolamide is in preventing attacks, prospective studies still have to prove whether it can prevent progressive ataxia in EA-2 or even improve chronic cerebellar deficits.
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PMID:Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). 939 Aug 41

A 39-year-old man with episodic ataxia with nystagmus (EA-2) was reported. He showed intermittent cerebellar dysfunction, i.e., ataxia, nystagmus, dysarthria and vertigo, since he was 10 years old. Although this attack lasted for several hours, he was normal with exception of interictal nystagmus. His parents and sister showed no episodic ataxia. We ruled out the diseases, which may cause episodic ataxia, such as multiple sclerosis, vascular disorders, metabolic disorders and congenital anomalies. He was released from the attack by treatment with acetazolamide. EA-2 has been associated with mutations in the alpha 1A-voltage dependent calcium channel gene (CACNL1A4), which is also affected in familial hemiplegic migraine (FMH) and spinocerebellar ataxia type 6 (SCA6). In EA-2, frame-shift mutation leading to premature stop and splice-site mutation leading to truncated, non-functional channel protein have been reported. However, our patient did not have the mutations in the CACNL1A4 gene that were previously reported. In addition, our patient did not have an expanded CAG allele in the CACNL1A4 gene which is responsible for SCA6. Further examination is required to address whether a new mutation exists in the CACNL1A4 gene in our patient.
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PMID:[A sporadic case of episodic ataxia with nystagmus (EA-2)]. 980 92

Spinocerebellar ataxia type 6 (SCA6) is genetically defined as a group of SCA characterized by late-onset pure cerebellar ataxia clinically and by a small CAG repeat expansion in the gene encoding the alpha 1A-voltage-dependent-Ca channel subunit (CACNL1A4) on chromosome 19p13.1 genetically. We analyzed the initial symptoms and the mode of progression in this disorder on 25 genetically verified patients. The initial symptoms were recurrent episodes of transient vertigo (72%) or unsteady gait (28%). Neurologically, they showed apparent gaze-evoked nystagmus (92%), transient positional nystagmus (83%), and periodic alternating nystagmus (4%), in addition to cerebellar ataxia. In addition to these episodic symptoms, all patients developed progressive cerebellar ataxia over years. These fluctuating symptoms at the initial stage of the illness were clearly different from those of other SCA, rather overlapping with those of episodic ataxia type 2 (EA2), an allelic disorder of SCA6. The clinical similarity indicates that there might be a common mechanism at least in part causing these two disorders. The mode of progression and their neurological features were also presented.
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PMID:[Initial symptoms and mode of neurological progression in spinocerebellar ataxia type 6 (SCA6)]. 984 64

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.
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PMID:A patient homozygous for the SCA6 gene with retinitis pigmentosa. 1208 23

Spinocerebellar ataxia (SCA) is a group of heterogeneous disorders. In Japan, approximately 60% of SCA consist of sporadic disorders, and the rest mostly consists of a variety of late-onset dominant disorders. In the latter, MJD, SCA6, DRPLA, SCA1 and SCA2 are frequent in this order, and others are rare. All these disorders are caused by unstable expansion of CAG repeat in the coding region of each responsible gene. Among those disorders, SCA6 manifests late-onset pure cerebellar ataxia and frequently associated with positioning vertigo. In other disorders, phenotype variation, clinical severity, and onset of age are known to correlate inversely with the CAG repeat size. Such variation even in a given disorder is often difficult to apply single criteria to diagnose the disorder based on its clinical findings alone. MSA is a major disorder of sporadic SCA. Signs of cerebellar ataxia, parkinsonism, autonomic disturbance are incorporated into current diagnostic criteria. However, cases meeting the criteria of autonomic disturbances are confined to the advanced stage of the illness or rare cases starting with obvious dysautonomia. These problems indicate that the criteria need further adjustment.
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PMID:[Differential diagnosis of spinocerebellar ataxia]. 1278 68

In order to clarify the clinical and genetic features of SCA6, we retrospectively analyzed 140 patients. We observed an inverse correlation between the age of onset and the length of the expanded allele, and also between the age of onset and the sum of CAG repeats in the normal and the expanded alleles. The ages of onset of four homozygous patients correlated better with the sum of CAG repeats in both alleles rather than with the expanded allele calculated from heterozygous SCA6 subjects. Clinically, unsteadiness of gait was the main initial symptom, followed by vertigo and oscillopsia, and cerebellar signs were detected in nearly 100% of the patients. In contrast, extracerebellar signs were relatively mild and infrequent. The results of neuro-otological examination performed in 22 patients suggested the purely cerebellar abnormalities of ocular movements in nature. There was a close relationship between downbeat positioning nystagmus (DPN) and positioning vertigo, which became more common in the later stage. We conclude that total number of CAG repeat-units in both alleles is a good parameter for assessment of age of onset in SCA6 including homozygous patients. In addition, clinical and neuro-otological examinations suggested that SCA6 is a disease with predominantly cerebellar dysfunction.
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PMID:A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6. 1536 69

Onset of genetically determined neurodegenerative diseases is difficult to specify because of their insidious and slowly progressive nature. This is especially true for spinocerebellar ataxia (SCA) because of varying affection of many parts of the nervous system and huge variability of symptoms. We investigated early symptoms in 287 patients with SCA1, SCA2, SCA3, or SCA6 and calculated the influence of CAG repeat length on age of onset depending on (1) the definition of disease onset, (2) people defining onset, and (3) duration of symptoms. Gait difficulty was the initial symptom in two-thirds of patients. Double vision, dysarthria, impaired hand writing, and episodic vertigo preceded ataxia in 4% of patients, respectively. Frequency of other early symptoms did not differ from controls and was regarded unspecific. Data about disease onset varied between patients and relatives for 1 year or more in 44% of cases. Influence of repeat length on age of onset was maximum when onset was defined as beginning of permanent gait disturbance and cases with symptoms for more than 10 years were excluded. Under these conditions, CAG repeat length determined 64% of onset variability in SCA1, 67% in SCA2, 46% in SCA3, and 41% in SCA6 demonstrating substantial influence of nonrepeat factors on disease onset in all SCA subtypes. Identification of these factors is of interest as potential targets for disease modifying compounds. In this respect, recognition of early symptoms that develop before onset of ataxia is mandatory to determine the shift from presymptomatic to affected status in SCA.
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PMID:Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. 1875 44

Spinocerebellar ataxia type 6 (SCA6) is a calcium channelopathy due to a pathological CAG repeat expansion in CACNL1A4. Patients frequently describe paroxysmal vertigo early in the disease course, but it is not clear whether this is central or labyrinthine in origin. To address this issue we studied 21 SCA6 patients. Symptoms of vertigo were defined using a structured questionnaire. Signs were recorded during a standardised bed-side vestibular examination that included systematic positional testing with Frenzel goggles.Brief, recurrent attacks of vertigo occurred in 13 patients, usually preceding the onset of ataxia. Nystagmus was observed behind Frenzel goggles in 14 patients, and was induced either during positional testing, or head shaking in 20 patients. Only one patient had findings typical of benign paroxysmal positional vertigo (BPPV). Combined downbeat and horizontal gaze-evoked nystagmus ("side-pocket") was the most common form, occurring most commonly in supine and head-hanging positions, and following horizontal head-shaking. Nystagmus beating away from the ground (apogeotropic) occurred in 9 patients as they lay on their side.In conclusion, vertigo and abnormalities on bedside vestibular examination are common in SCA6, with forms of nystagmus typical of cerebellar, rather than labyrinthine, disease. These findings demonstrate phenotypic overlap between SCA6 and episodic ataxia type 2, which are both due to mutations in CACNL1A4.
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PMID:Vertigo and vestibular abnormalities in spinocerebellar ataxia type 6. 1922 13