Co-occurrence of Down Syndrome and Multiple Sclerosis.

Object: Down syndrome (DS) is often associated with autoimmune diseases; however, its association with multiple sclerosis (MS) has rarely been reported. In a previous report, the coincidence of DS and MS showed a negative association. Here, we searched for the coincidence of DS and MS, and attempted to resolve this negative association, focusing on the gene dosage effect, by utilizing available reports.

Case presentation: A 44-year-old woman with DS experienced a progressively worsening gait at onset. Auto-immuno-antibodies including aquaporin-4 antibody were negative. On the basis of brain magnetic resonance image (MRI) findings, the patient was diagnosed with possible MS. After three years, the patient demonstrated additional signs and regression symptoms. Re-examined brain MRI showed multiple new focal lesions. Based on the McDonald criteria, the patient was diagnosed with laboratory-supported defined MS.

Discussion: To date, we have found only one case report in the literature describing the development of MS in a 49-year-old man with DS. The protective effect of DS against the development of MS might be mediated by a gain of function due to a gene dosage effect, and the effect of candidate antigens could be interferon alpha and beta receptors, S100B, and amyloid precursor protein (APP).

Conclusions: In patients with DS, S100B and APP overexpression could protect against MS, but both correlate with the progression of Alzheimer's neuropathological changes. S100B and APP can be seemed to be multiple pathogenesis and co-occurrence of MS with DS and Alzheimer's dementia may advance more severely than MS without DS.