Maternal homozygosity for the common MTHFR mutation as a potential risk factor for offspring with limb defects.

A common mutation, C677T, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene leads to altered homocysteine metabolism, and has been associated with the occurrence of neural tube defects (NTD). Administration of folic acid decreases this risk. There is also evidence that periconceptional supplementation of mothers with folic acid can decrease the risk of limb defects in the offspring. Here we describe a child with a transverse terminal defect of one hand, whose mother is homozygous for the C677T MTHFR mutation. We suggest that homozygosity for the MTHFR mutation may be a risk factor for transverse terminal limb defect/s by an effect mediated through altered folate and homocysteine metabolism. Further studies of mothers of infants with limb reduction defects for the MTHFR mutation may be of help in establishing this association. A simple intervention in the form of folic acid supplementation would be protective, should an association be established.