Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6

Abstract

We describe two patients who suffered transient neonatal diabetes mellitus (TDNM), due to paternal isodisomy of chromosome 6. One patient, now 5 years old, had severe intra-uterine growth retardation, but recovered normal growth parameters. The other patient, currently 12 years old, had a normal birth weight but showed impaired post-natal growth; in addition to TNDM the patient presented with cardiac and thyroid abnormalities. These cases may suggest that the clinical phenotype of TNDM is more variable than previously believed. The contribution of genetic and epigenetic factors needs to be determined to elucidate the phenotype-genotype relationships of this disease.

Transient neonatal diabetes, a disorder of imprinting

“…However the latter patient, who died at 16 days of age, also had neonatal diabetes. There have now been a further 18 cases reported with paternal UPD(6) and TND [15][16][17][18][19][20][21][22][23] and it has been found to account for 50% of sporadic cases tested. 20 In 1996, Temple et al 24 discovered that paternal (and not maternal) transmission of a visible duplication of chromosome 6q24 could also lead to TND and this was reproduced in several studies including that of Cave et al, 17 who discovered a paternal 6q24 duplication in six of 13 cases with TND.…”

The Role of Imprinted Genes in Fetal Growth

“…Most TNDM cases have been associated with abnormalities involving paternal chromosome 6, including UPD [35][36][37][38][39][40] and duplications of partial 6q22-q24 UPD of the of paternally derived chromosome 6 [41,42]. All of the cases of UPD6 were isodisomies possibly due to a postzygotic duplication of the paternal chromosome 6; individuals with maternal UPD6 are not affected by TNDM [43], but 1 case of maternal UPD6 without TNDM had IUGR with postnatal catch-up growth [44].…”

Major difference in aetiology and phenotypic abnormalities between transient and permanent neonatal diabetes

“…The classical features of transient ND include macroglossia 16 18 and umbilical hernia 3 4 16 19-22 (table 3). Other defects arising in the patients in this report show a larger than expected number of congenital abnormalities in transient ND 13 that may be related to the nature of the genetic and epigenetic alterations involved. 4 6 7 Congenital malformations in patients with permanent ND are different from those of transient ND with combinations including organs derived from branching to the main visceral tube 23 (table 3).…”