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Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy.Other neurological features subsequently emerged,and"DIDMOAD"(Diabetes Insipidus,Diabetes mellitus,Optic Atrophy,and Deafness)became a commonly accepted acronym. Here we describe four further cases from two families,in whom there occurred previously unrecognized neurological features,central apnea and neurogenic upper airway collapse,together precipitating primary respiratory failure(fatal in one case),startle myoclonus(in two unrelated cases),axial rigidity and Parinaud's syndrome.MR images revealed striking brainstem atrophy affecting in particular the pons and midbrain.The mitochondrial DNA from three cases(and relatives)showed no evidence of any of the previously reported abnormalities.These neurological and neuroradiological features,in conjunction with(1)analyses showing the neurodegenerative origin of optic atrophy,deafness,diabetes insipidus,and incontinence,(2)other previously 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 neurodegenerative disorder with prominent optic atrophy and diabetes mellitus. |
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