So far this condition has been found in patients who first present with 6q24 transient neonatal diabetes.
Some features that have been noted in more than one patient with hypomethylation syndrome include:
- Poor growth during pregnancy
- Macroglossia (Large tongue)
- Umbilical Hernia (hernia around the belly button)
- Congenital heart anomaly
- Minor hand abnormalities such as a bend or curvature of the fifth fingers (the "little fingers") toward the adjacent fourth fingers called clinodactyly.
- Developmental delay. (In two patients this has been severe and associated with hypoplasia of the corpus callosum, cerebral blindness and in one profound hearing loss.)
It has been reported that some siblings have been found to have this condition. But more research is required to establish how this condition is inherited.
Genetic Causes
This was first described by the Wessex Imprinting group in 2006 and is currently being actively investigated. It was discovered because patients with transient neonatal diabetes due to loss of maternal methylation at 6q24 (see Transient Neonatal Diabetes page) were subsequently found to have a problem in the ‘silencing’ of other imprinted genes so this is a more generalised disorder. Sometimes this condition is due to a fault in a control gene called ZFP57 – this gene regulates the imprinting mechanism.
References for Hypomethylation Syndrome
- Mackay DJ, Callaway JL, Marks SM, White HE, Acerini CL, Boonen SE, Dayanikli P, Firth HV, Goodship JA, Haemers AP, Hahnemann JM, Kordonouri O, Masoud AF, Oestergaard E, Storr J, Ellard S, Hattersley AT, Robinson DO, Temple IK. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. Nat Genet. 2008 Aug;40(8):949-51. Epub 2008 Jul 11. PubMed citation
- Mackay DJ, Boonen SE, Clayton-Smith J, Goodship J, Hahnemann JM, Kant SG et al. A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. Hum Genet 2006; 120(2):262-269.
- Mackay DJ, Hahnemann JM, Boonen SE, Poerksen S, Bunyan DJ, White HE et al. Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus. Hum Genet 2006; 119(1-2):179-184.
- Boonen SE, Porksen S, Mackay DJ, Oestergaard E, Olsen B, Brondum-Nielsen K et al. Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. Eur J Hum Genet 2008; 16(4):453-461.