Monogenic Causes of Strokes

Abstract

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

Clinical exome sequencing uncovers a high frequency of Mendelian disorders in infants with stroke: A retrospective analysis

“…Pediatric stroke sometimes occurs as part of an inherited genetic syndrome (Barrett and Meschia, 2014), and can follow Mendelian inheritance patterns (Ilinca et al, 2020). Monogenic causes of stroke include CADASIL, homocystinuria, Fabry disease, TREX1 , COL4A1/COL4A2 ‐related syndromes, and others (Chojdak‐Łukasiewicz et al, 2021; Bersano et al, 2021). One study of 38 patients with pediatric and perinatal stroke diagnosed 10% of cases using a panel of 15 genes focused on Mendelian causes of stroke (Grossi et al, 2020).…”

Clinical exome sequencing for stroke evaluation uncovers a high frequency of Mendelian disorders: a retrospective analysis

“…Pediatric stroke sometimes occurs as part of an inherited genetic syndrome[2], and can follow Mendelian inheritance patterns[3]. Monogenic causes of stroke include CADASIL, homocystinuria, Fabry disease, TREX1, COL4A1/COL4A2 -related syndromes, and others[4, 5]. One study of 38 patients with pediatric and perinatal stroke diagnosed 10% of cases using a panel of 15 genes focused on Mendelian causes of stroke[6].…”

Special Issue: “Genomics of Stroke”

“…The monogenic causes of stroke are recognizable by key clinical features and radiographic pictures. Genetic tests are expensive but should be part of routine diagnostic procedures in younger patients with cerebrovascular events, especially in the absence of typical vascular risk factors [ 14 ]. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); Fabry disease; mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS); many single-gene diseases associated particularly with the cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS).…”

“…The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); Fabry disease; mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS); many single-gene diseases associated particularly with the cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this review, the clinical phenotypes for the most important single-gene disorders associated with strokes are presented [ 14 ]. The authors conclude that early diagnosis of the monogenic causes of stroke is important to provide appropriate therapy when available [ 14 ].…”

“…In this review, the clinical phenotypes for the most important single-gene disorders associated with strokes are presented [ 14 ]. The authors conclude that early diagnosis of the monogenic causes of stroke is important to provide appropriate therapy when available [ 14 ].…”