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

A mother and son suffer from hemiplegic migraine with onset in childhood. Both have nystagmus which has not changed for many years, but the date of onset is uncertain. They have an asymmetrical tremor, clinically indistinguishable from essential tremor. Neuroophthalmological examination revealed inability to produce smooth pursuit, gaze-paretic nystagmus, rebound nystagmus, failure of fixation suppression of the vestibuloocular reflex both horizontally and vertically, and low gain of the optokinetic system. These abnormalities, confirmed by electrooculography, are commonly seen in disease of the cerebellum and brainstem. Treatment with propranolol and pizotyline lessened the number of episodes of hemiplegia and improved the tremor. Hemiplegic migraine has been reported in association with nystagmus, retinal degeneration, deafness, and ataxia in varying combinations in three other families with autosomal dominant inheritance. These associated neurological manifestations likely represent system degenerations rather than the effect of repeated ischemia imputable to the migraine itself. The syndrome of hemiplegic migraine, tremor, and ocular smooth pursuit system disorder seen in this family appears to be inherited as a single autosomal dominant trait, although more than one autosomal dominant gene may be involved.
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PMID:An autosomal dominant syndrome of hemiplegic migraine, nystagmus, and tremor. 743 78

Hereditary paroxysmal cerebellar ataxia (HPCA) is an autosomal dominant disorder characterized by the recurrence of intermittent attacks of vestibulocerebellar ataxia lasting from 15 minutes to a few days. The number of attacks is often significantly decreased by acetazolamide treatment. Neurological examination shows a permanent gaze-evoked nystagmus, as well as a mild cerebellar ataxia in most patients. The paroxysmal feature of this condition is shared by another autosomal dominant neurological condition, familial hemiplegic migraine (FHM), a condition in which permanent cerebellar signs have also been reported in some families. Although hemiplegic migraine has never been reported in patients with HPCA, we hypothesized, based on the latter observations, that HPCA and FHM may be allelic disorders. We previously mapped a gene responsible for FHM on the short arm of chromosome 19. We performed linkage analysis with 6 markers spanning the FHM interval on a large HPCA family. Significant lod scores were obtained with 3 markers: D19S244 (LS = 3.71), D19S221 (3.60), and D19S226 (3.54) at theta = 0. Haplotype and multipoint linkage analysis established that the most likely location was the same interval of 30 cM encompassing the chromosome 19 FHM locus.
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PMID:A gene for hereditary paroxysmal cerebellar ataxia maps to chromosome 19p. 753 34

By analogy with ophthalmic migraine, hemiplegic migraine is defined by the occurrence during the attacks of unilateral weakness. This simple definition is however far from reflecting the wide range of clinical situations reported under this term. Familial hemiplegic migraine (FHM) is a well individualized autosomal dominant condition. Attacks start in childhood, adolescence, or early adulthood. They invariably include a unilateral weakness lasting 30 to 60 minutes and almost always associated with visual, sensory, or speech disturbances. They are occasionally very severe with a dense hemiplegia, confusion, coma or fever, but they always completely recover. Brain neuroimaging is normal. In 20% of the families, migraine is associated with permanent neurological signs, mainly nystagmus and cerebellar ataxia. FHM is a genetically heterogeneous condition, with half of the families linked to chromosome 19 and the other half in which this link is excluded. By contrast to FHM, which is a well defined entity, other varieties of so called hemiplegic migraine do not deserve to be individualized as such. They include attacks of migraine with typical aura when a unilateral weakness is part of the aura, severe hemiplegic attacks similar to those reported in FHM but sporadic, migrainous infarcts with hemiplegia, and, for some authors, alternating hemiplegia of childhood. The pathogenesis of all these conditions and of migraine itself remaining largely unknown, it is currently impossible to know whether or not they share common pathophysiologic mechanisms. The identification of the gene on chromosome 19 and the discovery of other genes will be major steps to elucidate this question.
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PMID:[Hemiplegic migraine]. 789 22

Familial hemiplegic migraine (FHM) is an autosomal dominant disorder characterized by transient hemiplegia during the aura phase of a migraine attack. Nystagmus has been reported in individuals affected with this disorder, but the origin of the ocular motility findings is unknown. A three-generation family with FHM is described and clinical histories are outlined. Ocular motility evaluations were performed on 7 family members, 5 with a history of hemiplegic migraine and 2 without history of migraine. All affected family members had abnormal eye movements consistent with vestibulocerebellar dysfunction. Magnetic resonance imaging scans in affected family members revealed cerebellar vermian atrophy. DNA linkage analysis revealed a common marker in all the affected family members on chromosome 19. We suggest that the hemiplegic migraine attacks and the cerebellar degeneration are linked genetically and that the eye movements are not the ischemic sequelae of recurrent migraine. Strikingly similar ocular motility findings and cerebellar degeneration are reported in both FHM and a genetically related disorder, hereditary paroxysmal cerebellar ataxia (HPCA). The significance of these similarities is discussed along with a proposed pathophysiology for FHM.
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PMID:Familial hemiplegic migraine, nystagmus, and cerebellar atrophy. 857 54

Point mutations of the CACNA1A gene coding for the alpha 1A voltage-dependent calcium channel subunit are responsible for familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA2). In addition, expansions of the CAG repeat motif at the 3' end of the gene, smaller than those responsible for dynamic mutation disorders, were found in patients with a progressive spinocerebellar ataxia, named SCA6. In the present work, the analysis of two new families with small CAG expansions of the CACNA1A gene is presented. In one family, with a clinical diagnosis of EA2, a CAG23 repeat allele segregated in patients showing different interictal symptoms, ranging from nystagmus only to severe progressive cerebellar ataxia. No additional mutations in coding and intron-exon junction sequences in disequilibrium with the CAG expansion were found. In the second family, initially classified as autosomal dominant cerebellar ataxia of unknown type, an inter-generational allele size change showed that a CAG20 allele was associated with an EA2 phenotype and a CAG25 allele with progressive cerebellar ataxia. These results show that EA2 and SCA6 are the same disorder with a high phenotypic variability, at least partly related to the number of repeats, and suggest that the small expansions may not be as stable as previously reported. A refinement of the coding and intron-exon junction sequences of the CACNA1A gene is also provided.
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PMID:Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. 930 78

Clinical details are given of different types of episodic ataxia: type 1, with myokymia, and attacks which usually last a few minutes, and may occur several times a day, and treatment with acetazolamide can reduce the number of attacks; type 2, with interictal nystagmus, and attacks which last for several hours to a day or more, and treatment with acetazolamide is very effective; paroxysmal choreoathetosis with episodic ataxia, with attacks lasting for about 20 min and occurring at varying intervals; and familial hemiplegic migraine, with transient hemiplegia presenting during the aura of a migraine headache, the symptoms improving on treatment with acetazolamide. Their inheritance is of dominant type; and the gene for type 1 is mapped to chromosome 12p near to a cluster of potassium channel genes, and that for type 2 and for familial hemiplegic migraine to chromosome 19p near to calcium channel genes. The differential diagnosis from other conditions with a periodic symptomatology is discussed, especially from a number of metabolic disorders. Treatment is effective for many of these, and the treatment of the episodic ataxias with acetazolamide can sometimes have a dramatic effect. The possible role of the channelopathies in the causation of some periodic neurological disorders is considered; with the expectation that further research will improve the identification of specific diseases, and lead to more effective treatment.
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PMID:Episodic ataxia and channelopathies. 953 53

The SCA6 mutation, a small expansion of a CAG repeat in a calcium channel gene CACNA1A, was identified in three pedigrees. Point mutations in other parts of the gene CACNA1A were excluded and new clinical features of SCA6 reported--namely, central positional nystagmus and episodic ataxia responsive to acetazolamide. The three allelic disorders, episodic ataxia type 2, familial hemiplegic migraine, and SCA6, have overlapping clinical features.
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PMID:Spinocerebellar ataxia type 6 with positional vertigo and acetazolamide responsive episodic ataxia. 977 87

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

Familial episodic ataxias are unusual hereditary disorders of early onset characterized by recurrent episodes of ataxia. Most patients recover fully between attacks, but some may develop progressive ataxia with cerebellar atrophy. There are two subtypes of episodic ataxia: type 1 (EA1), with interictal myokymia, and type 2 (EA2), with interictal nystagmus. Stress and fatigue can trigger ataxic spells, which can be responsive to acetazolamide. These clinical features are reminiscent of other channelopathies or paroxysmal neurologic disorders with progressive features caused by ion channel mutations. Familial episodic ataxias indeed are channelopathies. EA1 is caused by mutations in a potassium channel-encoding gene, whereas EA2 is caused by mutations in a calcium channel-encoding gene, which is also the disease-causing gene in spinocerebellar ataxia type 6 and several kindreds with familial hemiplegic migraine. Treatment with acetazolamide can be effective in decreasing the frequency of attacks and is generally well tolerated. Understanding the mechanism of action of acetazolamide and the functional consequences of these mutations will help one to develop a rational pharmacologic treatment for these disorders, which may share similar mechanisms with benign recurrent vertigo and more common forms of migraine.
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PMID:Familial Episodic Ataxias and Related Ion Channel Disorders. 1109 68

We describe an Italian family with familial hemiplegic migraine (FHM), subtle cerebellar signs and probable linkage to chromosome 1. FHM is genetically heterogeneous; in about 50% of families it is caused by mutations within the CACNA1A gene on chromosome 19. Linkage to 1q31 and 1g21-23 has also been established. Other families do not link either to chromosome 19 or 1. Chromosome 19-linked FHM may display nystagmus and cerebellar ataxia. Affected family members were neurologically examined; linkage analysis was performed with markers for chromosomes 19p13, 1q21-23, and 1q32. Five family members had hemiplegic migraine, and 3 displayed additional cerebellar signs (scanning speech and nystagmus). In 1 patient, episodes of hemiplegic migraine triggered by mild head trauma. Epilepsy and mental retardation were also found in 1 affected relative each. Lod scores for linkage to 19p13 were negative, while the maximum two-point lod score was 1.81 to 1q21-23. This family with FHM and associated subtle cerebellar signs, epilepsy and mental retardation showed probable linkage to 1q21-23.
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PMID:Familial hemiplegic migraine: clinical features and probable linkage to chromosome 1 in an Italian family. 1211 14


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