IllnessCADASIL, differential diagnosis

NGS +

[Sanger]

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL, is a hereditary disease that causes transient ischaemic attacks and strokes. This disease affects the blood flow in the small blood vessels, especially in the brain, but also in the heart, kidneys, eyes and peripheral nerves. The smooth muscle cells of the vessels are dysfunctional and gradually die. Cerebral arteriopathy can cause migraines, often with visual sensations and auras or epilepsy. The damaged blood vessels reduce the blood flow, eventually from childhood to late adulthood, but typically in the middle adulthood. CADASIL patients often suffer multiple strokes. Recurrent infarctions damage the brain over time. Strokes in the subcortical area can lead to progressive dementia and changes in mood and personality. Many ppatients with CADASIL also develop leukoencephalopathy. The age at first onset of symptoms varies widely among affected individuals, as does the severity of these signs. Mutations in the NOTCH3 gene cause CADASIL and lead to apoptosis of vascular smooth muscle cells. CADASIL is inherited in an autosomal dominant manner. The differential diagnosis of clinically suspected CADASIL includes sporadic or multifactorial (e.g. multiple sclerosis) and hereditary diseases (Fabry disease, CARASIL, CARASAL, MELAS, etc.). Since the molecular genetic yield rarely exceeds 15% of suspected cases, a negative DNA test result does not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1500/

• DD: CARASAL, cathepsin A–related arteriopathy, strokes, leukoencephalopathy
• Alias: Familial cerebral small vessel disease
• Allelic: Aicardi-Goutieres syndrome 1, AD + AR (TREX1)
• Allelic: Alzheimer disease 1, familial (APP)
• Allelic: Anterior segment dysgenesis 3, multiple subtypes (FOXC1)
• Allelic: Arterial calcification, generalized, of infancy, 2 (ABCC6)
• Allelic: Axenfeld-Rieger syndrome, type 3 (FOXC1)
• Allelic: Chilblain lupus (TREX1)
• Allelic: Developemental + epileptic encephalopathy 42 (CACNA1A)
• Allelic: Ehlers-Danlos syndrome, vascular type (COL3A1)
• Allelic: Episodic ataxia, type 2 (CACNA1A)
• Allelic: Fabry disease, cardiac variant (GLA)
• Allelic: Lateral meningocele syndrome (NOTCH3)
• Allelic: Macular degeneration, age-related, neovascular type; Macular degen., age-rel., 7 (HTRA1)
• Allelic: Myofibromatosis, infantile 2 (NOTCH3)
• Allelic: Retinal arteries, tortuosity of (COL4A1)
• Allelic: Spinocerebellar ataxia 6 (CACNA1A)
• Allelic: Systemic lupus erythematosus, susceptibility to (TREX1)
• Alternating hemiplegia of childhood 1 (ATP1A2)
• Angiopathy, hereditary, with nephropathy, aneurysms + muscle cramps (COL4A1)
• Brain small vessel disease 2 (COL4A2)
• Brain small vessel disease 3 (COLGALT1)
• Brain small vessel disease with/-out ocular anomalies (COL4A1)
• CARASIL syndrome (HTRA)
• Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants (APP)
• Cerebral arteriopathy with subcortical infarcts + leukoencephalopathy 1 (NOTCH3)
• Cerebral arteriopathy, AD, with subcortical infarcts + leukoencephalopathy, type 2 (HTRA1)
• Fabry disease (GLA)
• Galactosialidosis (CTSA)
• Hemorrhage, intracerebral, susceptibility to (COL4A1, COL4A2)
• Microangiopathy + leukoencephalopathy, pontine, AD (COL4A1)
• Migraine, familial basilar (ATP1A2)
• Migraine, familial hemiplegic, 1 (CACNA1A)
• Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Migraine, familial hemiplegic, 2 (ATP1A2)
• Polymicrogyria with/-out vascular-type EDS (COL3A1)
• Pseudoxanthoma elasticum (ABCC6)
• Pseudoxanthoma elasticum, forme fruste (ABCC6)
• Vasculopathy, retinal, with cerebral leukoencephalopathy + systemic manifestations (TREX1)