Familial occipital calcifications, hemorrhagic strokes, leukoencephalopathy, dementia, and external carotid dysplasia

Objective: To describe a new familial association of late-onset dementia, p atchy leukoencephalopathy, intracerebral hemorrhages, bilateral occipital c alcifications (BOC), and external carotid artery dysplasia (ECAD). Methods: At age 62, the proband, who was of Spanish descent, had left temporal hemo rrhage in a background of progressive mental deterioration. Neuroimaging re vealed fine tram-fine BOG, extensive leukoencephalopathy, and bilateral ECA D. Biologic screening for celiac disease was negative. Skin biopsy with ult rastructural study revealed heretofore unreported changes in the basal lami na of capillaries, with multilayered appearance and round-shaped microcalci fications. Of 19 next-of-kin who survived beyond 60 years of age, six had b rain disorders; four of the six presented at least three components of the syndrome. The proband's mother had died at age 83 with profound dementia; o ne sister, who was diagnosed with dementia with BOC and leukoencephalopathy at age 67, died 2 years later from intracerebral hemorrhage; a brother had an occipital hemorrhage at age 58, at which time BOC and leukoencephalopat hy were discovered; and another brother died after a minor stroke at age 70 with dementia, leukoaraiosis, BOG, and ECAD. A proband's cousin also had a n unexplained ischemic stroke at age 55, but without other features of the entity. In no subject was there evidence of seizures, facial angioma, or in tracranial vascular malformation, and arterial hypertension was neither con stant nor severe. Conclusion: These clinical, neuroradiologic, and histolog ic features suggest a new familial cerebrovascular entity with widespread m icrovascular calcifications and autosomal (presumably dominant) inheritance . We suggest the acronym FOCHS-LADD, for familial occipital calcifications, hemorrhagic strokes, leukoencephalopathy, arterial dysplasia, and dementia .