Advances on the spectrum of neurological diseases related to the CACNA1A gene / 中华实用儿科临床杂志

The CACNA1A gene encodes a voltage-gated calcium channel of the pore-forming protein, which has important functions in the central nervous system.The CACNA1A gene mutation can lead to a variety of neurological diseases, including familial hemiplegic migraine 1, spinocerebellar ataxia 6, episodic ataxia 2 and early infantile epileptic encephalopathy 42.Overlapping phenotypes could be observed in a small number of patients.This review summarized the clinical and genetic characteristics of the CACNA1A gene mutation.

Clinical and Genetic Features of Familial Hemiplegic Migraine

Migraine is a common cause of episodic headache disorder, and multiple factors are associated with the pathogenic mechanism underlying migraine. Recent studies suggest that genetic determinants influence migraine, most likely as part of a multifactorial mechanism. Due to the similarity in clinical features and pathophysiological mechanisms between familial hemiplegic migraine (FHM) and migraine with aura, FHM can be used as a model for migraine and aura. Mutations in the CACNA1A gene on chromosome 19p13 (FHM1), in the ATP1A2 gene at 1q23 (FHM2), and in the SCNA1A gene at 2q24 (FHM3) are responsible for most of the representative types of FHM. The recent beta version of the third edition of the International Classification of Headache Disorders contains revised diagnostic criteria for FHM, which include the above-three genetic factors. In this review we discuss the clinical and genetic features of FHM.

Clinical and Genetic Features of Familial Hemiplegic Migraine

Migraine is a common cause of episodic headache disorder, and multiple factors are associated with the pathogenic mechanism underlying migraine. Recent studies suggest that genetic determinants influence migraine, most likely as part of a multifactorial mechanism. Due to the similarity in clinical features and pathophysiological mechanisms between familial hemiplegic migraine (FHM) and migraine with aura, FHM can be used as a model for migraine and aura. Mutations in the CACNA1A gene on chromosome 19p13 (FHM1), in the ATP1A2 gene at 1q23 (FHM2), and in the SCNA1A gene at 2q24 (FHM3) are responsible for most of the representative types of FHM. The recent beta version of the third edition of the International Classification of Headache Disorders contains revised diagnostic criteria for FHM, which include the above-three genetic factors. In this review we discuss the clinical and genetic features of FHM.

Migraña hemipléjica familiar / Familial hemiplegic migraine

Las cefaleas constituyen una causa frecuente de consulta en Pediatría, siendo la migraña el tipo más frecuente de las cefaleas primarias en la infancia. La asociación entre cefalea y hemiplejía aguda en la infancia pudiera corresponder a múltiples etiologías debiéndose considerar las de carácter hereditario. La migraña hemipléjica familiar se caracteriza por la presencia de crisis migrañosas con trastornos motores deficitarios transitorios, afasia o alteraciones sensitivas o sensoriales. Se describe el caso de una adolescente femenina de 12 años de edad, con antecedentes familiares de migraña, historia de cefalea migrañosa de un año de evolución, que cumple con los criterios establecidos por la Sociedad Internacional de Cefaleas de migraña hemipléjica familiar. El examen neurológico y los paraclínicos complementarios fueron normales. Se realizó tratamiento con flunarizina e ibuprofeno con evolución satisfactoria

Headaches are a frequent cause of consultation in Pediatrics, migraine being the most common type of primary headaches in children. The association between headache and acute hemiplegia in childhood may correspond to multiple etiologies, including those considered as inherited. Familial hemiplegic migraine is characterized by the presence of migraine crisis with transient motor deficit disorders, aphasia and sensitive or sensory disturbances. We describe the case of a 12 year-old girl with a family history of migraine, and migraine headache of a year of evolution, which meets the criteria established by the International Headache Society of Familial Hemiplegic Migraine. Neurological examination and the paraclinical studies were normal. She was treated with flunarizine and ibuprofen with satisfactory outcome

Familial Hemiplegic Migraine with Prolonged Coma and Cerebellar Atrophy: CACNA1A T666M Mutation in a Korean Family

We report the first Korean patient with familial hemiplegic migraine type 1, with clinical and multimodal imaging findings. A 43-yr-old man was admitted for right hemianopia and aphasia, followed by coma. MRI showed only cerebellar atrophy. CT angiography showed mild vasodilation of intracranial blood vessels and increased vascularity in the left hemisphere and perfusion-weighted imaging showed elevated cerebral blood flow. Gene analysis of the patient and his mother led to the identification of a heterozygous point mutation (1997C-->T, T666M) in exon 16 of the CACNA1A gene. Familial hemiplegic migraine should be considered in patients with episodic neurological dysfunction with cerebellar atrophy.

A Case of Familial Hemiplegic Migraine / 대한소아신경학회지

Familial hemiplegic migraine(FHM) is an autosomal dominant subtype of migraine with aura, characterized by the occurrence of hemiplegia during the aura. Two subforms of FHM families exist; pure FHM in 80% and FHM families with cerebellar symptoms in 20%. Half of the known FHM families show genetic linkage to chromosome 19p13, and in these families FHM is caused by missense mutations in a neuronal P/Q type calcium channel alpha-1 subunit gene(CACNA1A gene). Linkages to 1q31 and 1q21-23 have also been established. Other families are linked neither to chromosome 19 nor 1. Clinical variabilities are partially associated with the various types of CACNA1A gene mutations. FHM is distinguished from more frequent migraine types by a clear, dominant inheritance pattern and the relative absense of other headache types. Further investigation of FHM will help to clarify the genetics of more common migraine. We describe a male patient with FHM with a brief review of the literature.

Two Cases of Sporadic Hemiplegic Migraine / 대한소아신경학회지

Hemiplegic migraine is characterized by the occurrence of migraine attacks with unilateral weakness. The attack usually starts in childhood, adolescence, or early adulthood. The diagnosis may be delayed if there is no relevant family history. We experienced two cases of hemiplegic migraine of 8 and 14 years old girls whose neuroimaging studies including MRA showed no abnormal findings in the acute phases and the ictal EEG findings also revealed normal. The hemiplegic attacks associated with sensory disturbance were improved by calcium channel blocker(Flunarizine). Hemiplegic migraine should be considered in the differential diagnosis of a pediatric hemiparesis even if there is no familial migraine history.