Maternal MTHFR C677T genotype and septal defects in offspring with Down syndrome: A pilot study

  • GM Elsayed
  • SM Elsayed
  • SS Ezz-Elarab


Background: While abnormal folate/homocysteine metabolism has been implicated as an etiology for the development of both CHD and DS, recent studies and meta-analyses did not consider MTHFR C677T genotype as a maternal risk factor for either of these conditions alone.
Aim of work: To investigate if methylenetetrahydrofolate reductase (MTHFR) C677T genotype is a maternal risk factor for the development of congenital heart disease (CHD) only in children with Down syndrome (DS).
Subjects and methods: Molecular analysis of MTHFR C677T and serum folic acid was done for sixty-one consecutive mothers of children with CHD in the form of septal defects (26 with DS and 35 without DS) and another 61 mothers of apparently healthy children (without DS or CHD).
Results: The frequency of CT genotype was significantly higher in mothers of children with AV canal (whether in DS or non-DS) when compared to ASD and in mothers of DS with AV canal when compared to controls. The frequency of TT genotype was higher in mothers of DS with ASD than controls but statistically insignificant. In non-DS mothers, the distribution of the genotypes did not differ in relation to the type of CHD. The mean folic acid level did not differ between different study groups.
Conclusions: MTHFR 677CT genotype could be implicated as a maternal risk factor for septal defects especially in children with DS. Carriers of this genotype may have more risk of development of AV canal in their children. A major limitations of this study was the small sample size and so further studies on a larger sample of patients and their mothers in addition to measurement of homocysteine level in this population is needed to investigate this theory and to clarify the actual role of MTHFR polymorphism and the risk of development of CHD in DS.

Keywords: Congenital heart disease; Down syndrome; Folic acid; MTHFR genotype


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eISSN: 1110-8630