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) are described: one with paternal uniparental disomy for chromosome 6 and one with normal, biparental inheritance. The first child presented with low birth weight, macroglossia, hypertelorism, and club foot in addition to NDM. In this patient hyperglycemia was transient, and insulin treatment was discontinued at 4 months of age. The second child also presented with low birth weight but was normal in appearance, and insulin dependence continues after 5 years. Genetic analysis with polymorphic DNA markers for chromosome 6 indicated the presence of paternal uniparental disomy (UPD) in the first case 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, not usually associated with NDM. Therefore the simultaneous finding of NDM and macroglossia should be a strong indicator for genetic testing. The genetic finding of paternal UPD 6 allows prediction of a transient, rather than permanent, form of diabetes mellitus and no increased recurrence risk of transient NDM in subsequent pregnancies.