6q24 duplication and transient neonatal diabetes: a possible differential diagnosis with Beckwith-Wiedemann syndrome?

Paternal uniparental disomy of chromosome 6 (UPD6) is an important cause of transient neonatal diabetes (TND) and macroglossia. We observed a female patient born with macroglossia who had 2 episodes of transient hyperglycaemia in the neonatal period and with a negative test result for UPD6. The patient developed asymmetry of lower limbs, with the left limb more developed than the right one, and a hyperplasia of the left kidney upon follow-up. Detailed investigation on family history (not available earlier) disclosed the presence of diabetes and an undefined rearrangement of chromosome 6 in two first cousins of the proband's father. Karyotype analysis on the proband's lymphocytes was normal. We therefore carried out array-CGH analysis: this method revealed the presence of a 2 Mb duplication in 6q [dup(6)(q24.2q24.3)]. The same duplication was present in the unaffected father. This duplication seems to be responsible for the development of a clinical phenotype that has similarities with the Beckwith-Wiedemann syndrome (BWS). At birth, BWS children have macroglossia and TND, characterized by impaired insulin response to glucose but normal response to glucagon. Duplications of chromosome 6q have been observed in some cases of TND and the duplicated region on 6q usually undergoes maternal imprinting. This could explain why the proband's father and paternal uncle, both of whom should have inherited the duplicated chromosome from their mothers, did not manifest any symptoms of the condition. Only one other familial case has been reported in literature.