Methylenetetrahydrofolate reductase gene polymorphisms and neural tube defects epidemiology in the Slovak population.

BACKGROUND: Folate deficiency is a known factor contributing to the formation of neural tube defects (NTDs). Many folate metabolism gene variants have been investigated, but only a few substantial associations have been established, the C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene being one of the most significant. METHODS: We determine the MTHFR C677T and A1298C genotypes in 93 Slovak NTD patients and 290 control newborns with respect to sex and ethnicity. Furthermore, we summarize current data on the incidence and types of NTDs in Slovakia. RESULTS: The Slovak population frequencies of T allele and TT genotype of the C677T MTHFR gene polymorphism were 0.25 and 6.9%, respectively; similarly, those of the C allele and CC genotype of the A1298C polymorphism were 0.35 and 13.8%, respectively. No differences between the sexes and within ethnic groups were observed. In NTD patients, genotype analysis of the C677T polymorphism revealed 0.29 and 9.8% for T allele and TT genotype frequencies, respectively (p = 0.26; OR, 1.23; 95% CI, 0.84-1.81; resp. p = 0.36; OR, 1.46; 95% CI, 0.56-3.52) compared to the controls. The frequencies of C allele and CC genotype of A1298C polymorphism were 0.34 and 6.5%, respectively (p = 0.81; OR, 0.96; 95% CI, 0.66-1.38; resp. p = 0.06; OR, 0.44; 95% CI, 0.15-1.09). There were also no sex-related differences in genotypes distribution in NTD patients. CONCLUSIONS: No significant associations between the C677T and A1298C MTHFR gene polymorphisms and NTDs and no differences between the two main ethnic groups (white-Caucasians, Roma) were found in Slovakia. The total incidence of NTDs in Slovakia is, according to the official sources, 0.53/1000, and the incidence among liveborn newborns is 0.28/1000.

Familial microhydranencephaly, a family that does not map to 16p13.13-p12.2: relationship with hereditary fetal brain degeneration and fetal brain disruption sequence.

Microhydranencephaly (MHAC) is a serious developmental brain anomaly characterized by microcephaly with severe reduction of brain hemispheres and intracranial space filled with cerebrospinal fluid without signs of intracranial hypertension. Clinical findings are very similar to fetal brain disruption sequence - severe microcephaly, scalp rugae, and profound developmental delay; however, although fetal brain disruption sequence is a sporadic condition caused by an external disruptive event, familial cases of MHAC presumably result from a process of progressive brain damage also termed as 'hereditary fetal brain degeneration'. Familial occurrence of this phenotype is very rare - only three reports on four families have been published so far. Here we present two new patients - affected brothers from Slovakia - and provide an update on a previously described case from a Turkish Anatolian family. We also present data excluding linkage to an MHAC locus 16p13.13-p12.2 in the Slovak family. We compare clinical and imaging findings in all five families and suggest genetic heterogeneity for this condition. In genetic counseling for this phenotype, especially in the absence of any known teratogenic factors in pregnancy, we suggest that the possibility of recurrence should be considered.