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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a three generation family with recurrent strokes and cataracts. The index case, a 14 year old boy presented with stroke at the age of 14 years and again 6 months later. His mother had long standing episodic headaches diagnosed as migraine. Grandmother was initially diagnosed with multiple sclerosis and had recurrent strokes at age 18 years and 49 years. MRI scanning showed a diffuse leukoencephalopathy with microhaemorrhages in all three individuals. All of the family members had cataracts but did not have retinal arterial changes. Sequence analysis of COL4A1 revealed the heterozygous missense mutation c.2263G-->A in exon 30, responsible for a glycine-to-arginine substitution (p.Gly755Arg) in both the index case and mother. Grandmother died at the age of 73 years and DNA analysis was not possible. Mutation in COL4A1 should be considered in families with a history of autosomal dominant cerebral vasculopathy, even in the absence of porencephaly.
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PMID:A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly. 1947 66

Migraine is a complex, debilitating neurovascular disorder, typically characterized by recurring, incapacitating attacks of severe headache often accompanied by nausea and neurological disturbances. It has a strong genetic basis demonstrated by rare migraine disorders caused by mutations in single genes (monogenic), as well as familial clustering of common migraine which is associated with polymorphisms in many genes (polygenic). Hemiplegic migraine is a dominantly inherited, severe form of migraine with associated motor weakness. Family studies have found that mutations in three different ion channels genes, CACNA1A, ATP1A2, and SCN1A can be causal. Functional studies of these mutations has shown that they can result in defective regulation of glutamatergic neurotransmission and the excitatory/inhibitory balance in the brain, which lowers the threshold for cortical spreading depression, a wave of cortical depolarization thought to be involved in headache initiation mechanisms. Other putative genes for monogenic migraine include KCKN18, PRRT2, and CSNK1D, which can also be involved with other disorders. There are a number of primarily vascular disorders caused by mutations in single genes, which are often accompanied by migraine symptoms. Mutations in NOTCH3 causes cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebrovascular disease that leads to ischemic strokes and dementia, but in which migraine is often present, sometimes long before the onset of other symptoms. Mutations in the TREX1 and COL4A1 also cause vascular disorders, but often feature migraine. With respect to common polygenic migraine, genome-wide association studies have now identified single nucleotide polymorphisms at 38 loci significantly associated with migraine risk. Functions assigned to the genes in proximity to these loci suggest that both neuronal and vascular pathways also contribute to the pathophysiology of common migraine. Further studies are required to fully understand these findings and translate them into treatment options for migraine patients.
Headache 2017 Apr
PMID:Genetics of Migraine: Insights into the Molecular Basis of Migraine Disorders. 2961 Nov 88