Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy.
BACKGROUND
The main hereditary vascular conditions involving both retinal and cerebral vessels include cerebroretinal vasculopathy, HERNS (hereditary endotheliopathy with retinopathy, nephropathy, and stroke), and hereditary vascular retinopathy; all are linked to the same locus on chromosome 3p21. Hereditary retinal arteriolar tortuosity is a distinct, autosomal dominant condition characterized by retinal arteriolar tortuosity and recurrent retinal hemorrhages. This condition is known to affect only retinal vessels.


METHODS
Clinical and brain MRI investigations of eight members of a three-generation family and extensive biological and systemic vascular investigations within one affected family member were conducted.


RESULTS
Six of eight family members were clinically symptomatic; disorders included infantile hemiparesis (2), migraine with aura (3), and retinal hemorrhage (1). Five individuals had retinal arteriolar tortuosities. A diffuse leukoencephalopathy in association with dilated perivascular spaces was observed in six individuals. Two family members had silent, deep cerebral infarcts as demonstrated on MRI. Genetic linkage analysis strongly suggests that this disorder is not linked to the 3p21 hereditary vascular retinopathy/cerebroretinal vasculopathy/HERNS locus.


CONCLUSIONS
The authors describe a novel hereditary autosomal dominant condition affecting both retinal and cerebral vessels and characterized by infantile hemiparesis, migraine with aura, retinal hemorrhage, retinal arterial tortuosity, and leukoencephalopathy with dilatation of perivascular spaces and microbleeds on brain MRI. Investigation of additional families should help to map the gene and to better categorize the spectrum of hereditary cerebroretinal small vessel diseases.
Vahedi
K
K
Service de Neurologie, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Paris, France. katayoun.vahedi@lrb.ap-hop-paris.fr
Massin
P
P
Guichard
J-P
JP
Miocque
S
S
Polivka
M
M
Goutières
F
F
Dress
D
D
Chapon
F
F
Ruchoux
M-M
MM
Riant
F
F
Joutel
A
A
Gaudric
A
A
Bousser
M-G
MG
Tournier-Lasserve
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D001160:Arterioles / Q000002:abnormalities*; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D025063:Chromosome Disorders; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015897:Comorbidity; D005260:Female; D005451:Fluorescein Angiography; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology / Q000235:genetics; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D020325:Migraine with Aura / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology; D010291:Paresis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D012161:Retinal Artery / Q000002:abnormalities*; D012164:Retinal Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012166:Retinal Hemorrhage / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D017585:Ultrasonography, Doppler, Transcranial; D044465:White People / Q000235:genetics
C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch