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

OBJECTIVE: To describe a new familial association of late-onset dementia, patchy leukoencephalopathy, intracerebral hemorrhages, bilateral occipital calcifications (BOC), and external carotid artery dysplasia (ECAD). METHODS: At age 62, the proband, who was of Spanish descent, had left temporal hemorrhage in a background of progressive mental deterioration. Neuroimaging revealed fine tram-line BOC, extensive leukoencephalopathy, and bilateral ECAD. Biologic screening for celiac disease was negative. Skin biopsy with ultrastructural study revealed heretofore unreported changes in the basal lamina of capillaries, with multilayered appearance and round-shaped microcalcifications. Of 19 next-of-kin who survived beyond 60 years of age, six had brain 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; one 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 leukoencephalopathy were discovered; and another brother died after a minor stroke at age 70 with dementia, leukoaraiosis, BOC, and ECAD. A proband's cousin also had an unexplained ischemic stroke at age 55, but without other features of the entity. In no subject was there evidence of seizures, facial angioma, or intracranial vascular malformation, and arterial hypertension was neither constant nor severe. CONCLUSION: These clinical, neuroradiologic, and histologic features suggest a new familial cerebrovascular entity with widespread microvascular calcifications and autosomal (presumably dominant) inheritance. We suggest the acronym FOCHS-LADD, for familial occipital calcifications, hemorrhagic strokes, leukoencephalopathy, arterial dysplasia, and dementia.