Wolfram syndrome
Wolfram Syndrome WFS1
DIDMOAD
Clinical Features
Wolfram syndrome is the association of juvenile onset diabetes mellitus, diabetes insipidus, optic atrophy and deafness, also known as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Patients show diabetes mellitus followed by optic atrophy in the first decade, cranial diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts early in the third decade, and multiple neurological abnormalities early in the fourth decade. Other abnormalities include primary gonadal atrophy. Most patients eventually develop all complications of this progressive, neurodegenerative disorder. Diverse neurological symptoms in Wolfram syndrome include hearing loss, nystagmus, mental retardation, urinary tract atony, ataxia, peripheral neuropathy, dementia, and psychiatric illnesses. Psychiatric illness appears to occur in most cases of Wolfram syndrome and a predisposition for psychiatric disorders was proposed for heterozygous carriers.
Genetic Information
Wolfram syndrome is caused by mutations in the gene encoding wolframin (WFS1) on chromosome 4p. Another locus for the disorder has been mapped to 4q (CISD2 gene, WFS2).
Prevalence
The prevalence of Wolfram syndrome in the U.K. is 1 : 770 000.
Diagnostic
Indication
Method
1. Mutation analysis of the exon 8 with intronic primers of the WFS1 gene by direct DNA sequencing (frequent mutations)
2. Mutation analysis of the entire coding and flanking intronic regions with intronic primers of the WFS1 gene by direct DNA sequencing
Sample Requirement
2 - 4 ml EDTA-blood
Duration
2 - 4 weeks