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Table 1 Risk to other family members for each type of transient neonatal diabetes mellitus

From: Genomic imprinting in diabetes

Type of TNDM Risk to other family members
Paternal UPD Unlikely to recur in other family members
Inherited paternal duplication The risk to siblings of inheriting the same duplication and being at risk for TNDM and later diabetes is 50%. Offspring of individuals with duplications are at 50% risk of inheriting the duplication, but at risk for TNDM or later diabetes if only the allele is inherited from the father
Paternal chromosomal rearrangement Risks to family members depend on the particular rearrangement involved. For example, partial trisomy for 6q24 as a result of unbalanced inheritance of a paternal but not maternal balanced reciprocal translocation would include the TNDM phenotype
De novo duplication on the paternally inherited chromosome Some residual risk to siblings owing to the possibility of paternal gonadal or undetected somatic mosaicism for the duplication. Offspring of individuals with a de novo duplication have a 50% risk of inheriting the duplication, with offspring of males but not females at risk for TNDM or later diabetes
Imprinting mutation of the 6q24 DMR No familial recurrence has been reported. The causes of these mutations are not well understood and Temple and Mackay consider testing siblings of affected children for diabetes to be appropriate. The risk to offspring of females with imprinting center mutations may theoretically be increased but no empirical data are available to support or refute this hypothesis
Generalized HIL Over 50% have homozygosity or compound heterozygosity for ZFP57 mutations as determined by sequencing. There is a 25% recurrence risk in siblings of a child who has inherited two ZFP57 mutations from carrier parents. The penetrance is not known. The recurrence risk for other forms of HIL is not known because the cause(s) are not known
  1. Adapted from and described in further detail in [39]. Abbreviations: HIL, hypomethylation at imprinted loci; TNDM, transient neonatal diabetes mellitus; UPD, uniparental disomy.