Abstract:
Introduction. Congenital malformations of the central nervous system account for about 25% of all defects and
cause psychomotor retardation and pronounced neurological deficits in children. The etiology of congenital neural
tube defects remains unexplored until the end. The key role of folic acid in the genesis of neural tube defects is proved.
Objective. To study the molecular genetic markers of violation of folate cycle and exogenous risk factors in children
with spina bifida from multiple pregnancies and their siblings.
Materials and methods. A clinical and laboratory analysis of two cases of the open form of spina bifida in children
of multiple births was carried out at the Odessa Regional Children’s Hospital. To identify the etiology of the disease,
clarify the mechanism of inheritance and determine the cause of discordance of the twins used genealogical, genetic,
molecular and twin methods. Polymorphisms of MTHFR were investigated. To determine the metabolic disorders biochemical method (for the definition of folate levels and homocysteine in the blood) and clinical examination methods
were used in children with spina bifida, as well as their mothers and siblings.
Results. Presented clinical cases confirmed NTD belonging to the group of polygenic inherited disease with the
alleged maternal inheritance mechanism. In both cases, the impact of environmental factors related to the proven risk
factors for the various types of NTD of the fetus is realized: weighed down gynecological and obstetric history of mothers (cases of spontaneous abortions taking oral contraceptives, unbalanced diet and lack of vitamins, especially folic
acid and В12), SARS, hyperthermia in the first trimester of pregnancy, smoking during pregnancy, tumors of the female
reproductive system and breast cancer. Multiple pregnancy can be identified as an individual risk factor for NTD. In
the first case study of polymorphisms C677T and A1298C gene MTHFR did not reveal the presence of a mutation in
the gene neither in the proband nor in his mother and siblings. However, in this case could not be stated that there is
no genetic conditions of impaired folate metabolism. Mutations of other genes encoding enzymes of folate cycle, such
as methionine synthase reductase (MTRR) gene and MTR, encoding the amino acid sequence of the enzyme methionine
synthase, are possible. In second case, maternal and siblings heterozygous form of MTHFR polymorphism was detected, which resulted in thermolability and, accordingly, decrease the activity of the enzyme. This was a genetic basis and
compounded the effects of the risk factors that led to the formation of congenital malformations in both siblings of twins.
Conclusions. Taking into account the percentage of concordance for dizygotic twins with NTD and a large number
of hidden forms of malformation in-depth examination and supervision of all siblings (especially twins) of children with
open forms of spina bifida is needed. Identification of the closed form of spinal malformation in siblings at early age
will determine the timely provision of necessary medical aid and would hinder the development of neurological and
urological complications.
Description:
Кафедра Педиатрии N°1, Неонатопогии и Биоэтики, Одесский Национальный Медицинский Университет, Одесса, Украина
