WOLFRAM-SYNDROME - HEREDITARY DIABETES-MELLITUS WITH BRAIN-STEM AND OPTIC ATROPHY

Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Other neurologica l features subsequently emerged, and ''DIDMOAD'' (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly acce pted acronym. Here, we describe 4 further cases from 2 families, in wh om there occurred previously unrecognized neurological features, centr al apnea and neurogenic upper airway Collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic r esonance images revealed striking brainstem atrophy affecting, in part icular, the pens and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnor malities. These neurological and neuroradiological features, in conjun ction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other pre viously reported neurological complications (including anosmia, ataxia , epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurode generative disorder with prominent optic atrophy and diabetes mellitus .