Wolfram syndrome in twelve patients from a mountainous area where consanguineous unions are not unusual: phenotypical expression

Background: Wolfram first reported the combination of juvenile-onset diabetes mellitus (DM) and optic atrophy (OA) in 1938. With the discovery of two other essential components, diabetes insipidus (DI) and deafness (D), Wolfram syndrome (WS) is now also known by the acronym DIDMOAD. Other, less common, manifestations include renal tract abnormalities, neuropsychiatric disorders and hypogonadism. Objective: Aim of the present study was to evaluate WS phenotypical expression in a mountainous area of North-eastern Sicily, where consanguineous unions are not very unusual. Population and methods: We evaluate the clinical findings in a study population of 12 WS Caucasian patients from 7 couples and 5 unrelated families of North-eastern Sicily area. They are aged between 9 and 29 years (mean age 22.1 ± 5.6 years). In order to definitely confirm that the 12 patients included in the present study are the only WS individuals aged under 30 who are currently living in Messina district, we have contacted all the other Units of our region. Results: In all cases, DM was the earliest detected abnormality and its presentation occurred during the first decade with a medium age at diagnosis of 5.33 ± 3.11 years; conversely, diabetes insipidus and deafness occurred in a later period (mean age 14.9 ± 4.5 and 13.4 ± 6.8 years, respectively). Our series presented other less common clinical features, including psychiatric disorders, renal out-flow tract abnormalities, primary gonadal atrophy, and even bilateral cataract. In two patients, belonging to the same pedigree, we also observed two different congenital heart defects, one of which had been previously described in only one WS patient . Conclusions: a) In our series, diabetes mellitus onset was before 10 yrs in 11/12 patients and ten cases have already developed all four peculiar manifestations of WS by 26 yrs; b) the finding of a cardiac malformation in WS children might not be quite fortuitous.