Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus

Two patients who presented at birth with neonatal diabetes mellitus (NDM) a re described: one with paternal uniparental disomy for chromosome 6 and one with normal, biparental inheritance. The first child presented with low bi rth weight, macroglossia, hypertelorism, and club foot in addition to NDM. In this patient hyperglycemia was transient, and insulin treatment was disc ontinued at 4 months of age. The second child also presented with low birth weight but was normal in appearance, and insulin dependence continues afte r 5 years. Genetic analysis with polymorphic DNA markers for chromosome 6 i ndicated the presence of paternal uniparental disomy (UPD) in the first cas e and normal, biparental inheritance in the second case. Paternal UPD 6 has been reported in 8 previous cases of which 6 showed NDM. Three cases with paternal UPD 6 also included additional anomalies, such as macroglossia, no t usually associated with NDM. Therefore the simultaneous finding of NDM an d macroglossia should be a strong indicator for genetic testing. The geneti c finding of paternal UPD 6 allows prediction of a transient, rather than p ermanent, form of diabetes mellitus and no increased recurrence risk of tra nsient NDM in subsequent pregnancies.