Walsh & Hoyt: Progressive Optic Atrophy with Juvenile Diabetes Mellitus, Diabetes Insipidus, and Hearing Loss (DIDMOAD/Wolfram's Syndrome)

In 1938, Wolfram described a family in which four of eight siblings had diabetes mellitus and bilateral optic atrophy. Three of the four affected siblings subsequently developed neurosensory hearing loss and two developed neurogenic bladder. DeLawter later reported a patient with diabetes mellitus and optic atrophy in whom diabetes insipidus was subsequently diagnosed. Since these initial reports, about 300 cases have been recorded, with a prevalence of 1 in 770,000 in the United Kingdom. The hallmark of all these cases is the association of juvenile diabetes mellitus and progressive visual loss with optic atrophy, almost always associated with diabetes insipidus, neurosensory hearing loss, or both (hence the acronym DIDMOAD for diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). The progression and development of this syndrome are variable. Symptoms and signs of diabetes mellitus usually occur within the first or second decade of life and usually precede the development of optic atrophy. In several cases, however, visual loss with optic atrophy was the first sign of the syndrome. In the early stages, visual acuity may be normal despite mild dyschromatopsia and optic atrophy. In later stages, visual loss becomes severe, usually worse than 20/200, suggesting progression. Visual fields show both generalized constriction and central scotomas. Optic atrophy is uniformly severe, and there may be mild to moderate cupping of the disc.