TY - JOUR
T1 - Hereditary cerebral small vessel disease and stroke
AU - Søndergaard, Christian Baastrup
AU - Nielsen, Jørgen Erik
AU - Hansen, Christine Krarup
AU - Christensen, Hanne
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several monogenic hereditary diseases causing cerebral small vessel disease and stroke have been identified. The purpose of this systematic review is to provide a guide for determining when to consider molecular genetic testing in patients presenting with small vessel disease and stroke. CADASIL, CARASIL, collagen type IV mutations (including PADMAL), retinal vasculopathy with cerebral leukodystrophy, Fabry disease, hereditary cerebral hemorrhage with amyloidosis, and forkhead box C1 mutations are described in terms of genetics, pathology, clinical manifestation, imaging, and diagnosis. These monogenic disorders are often characterized by early-age stroke, but also by migraine, mood disturbances, vascular dementia and often gait disturbances. Some also present with extra-cerebral manifestations such as microangiopathy of the eyes and kidneys. Many present with clinically recognizable syndromes. Investigations include a thorough family medical history, medical history, neurological examination, neuroimaging, often supplemented by specific examinations e.g of the of vision, retinal changes, as well as kidney and heart function. However molecular genetic analysis is the final gold standard of diagnosis. There are increasing numbers of reports on new monogenic syndromes causing cerebral small vessel disease. Genetic counseling is important. Enzyme replacement therapy is possible in Fabry disease, but treatment options remain overall very limited.
AB - Cerebral small vessel disease is considered hereditary in about 5% of patients and is characterized by lacunar infarcts and white matter hyperintensities on MRI. Several monogenic hereditary diseases causing cerebral small vessel disease and stroke have been identified. The purpose of this systematic review is to provide a guide for determining when to consider molecular genetic testing in patients presenting with small vessel disease and stroke. CADASIL, CARASIL, collagen type IV mutations (including PADMAL), retinal vasculopathy with cerebral leukodystrophy, Fabry disease, hereditary cerebral hemorrhage with amyloidosis, and forkhead box C1 mutations are described in terms of genetics, pathology, clinical manifestation, imaging, and diagnosis. These monogenic disorders are often characterized by early-age stroke, but also by migraine, mood disturbances, vascular dementia and often gait disturbances. Some also present with extra-cerebral manifestations such as microangiopathy of the eyes and kidneys. Many present with clinically recognizable syndromes. Investigations include a thorough family medical history, medical history, neurological examination, neuroimaging, often supplemented by specific examinations e.g of the of vision, retinal changes, as well as kidney and heart function. However molecular genetic analysis is the final gold standard of diagnosis. There are increasing numbers of reports on new monogenic syndromes causing cerebral small vessel disease. Genetic counseling is important. Enzyme replacement therapy is possible in Fabry disease, but treatment options remain overall very limited.
KW - Alopecia
KW - Animals
KW - Brain
KW - Cerebral Infarction
KW - Cerebral Small Vessel Diseases
KW - Humans
KW - Leukoencephalopathies
KW - Spinal Diseases
KW - Stroke
KW - Journal Article
KW - Review
U2 - 10.1016/j.clineuro.2017.02.015
DO - 10.1016/j.clineuro.2017.02.015
M3 - Review
C2 - 28254515
SN - 0303-8467
VL - 155
SP - 45
EP - 57
JO - Clinical Neurology and Neurosurgery
JF - Clinical Neurology and Neurosurgery
ER -