Fetal growth restriction syndrome in patients with a GCK gene mutation

Hyperglycemia during pregnancy is a manifestation of pregestational and newly diagnosed diabetes mellitus (DM), which includes overt DM and gestational diabetes mellitus (GDM). A special and poorly understood issue in the structure of hyperglycemia during pregnancy is the monogenic forms of DM, which are mistakenly classified as GDM or overt DM and are first diagnosed during pregnancy. A mutation in the GCK (glucokinase) gene, the most common among monogenic forms of diabetes, has unique characteristics and requires insulin therapy only during pregnancy. In a fetus inheriting a pathogenic mutation in the GCK gene from its mother, mild hyperglycemia is not associated with macrosomia and, on the contrary, can be considered normal, ensuring adequate fetal growth. Insulin therapy in mothers with a GCK gene mutation is an independent risk factor for fetal growth restriction (FGR) and low birth weight infants. «Aggressive» reduction of maternal glycemia in the presence of a fetus with a mutation (insulin therapy with strict compensation parameters) combined with daily calorie restriction can negatively impact fetal growth and weight gain. However, the two clinical observations presented in this article demonstrate that fetal growth restriction in pregnant women with diabetes and a heterozygous mutation in the GCK gene is not always associated with the mutation itself, but can be explained by multiple factors, including the condition of the fetoplacental complex. These clinical observations highlight the importance of differential diagnosis of the causes of FGR and the significant role of timely fetal assessment using prenatal genetic diagnosis of GCK gene mutations, fetal Doppler ultrasound, and dynamic fetometry using standardized percentile scales recommended for the territories of the Russian Federation to determine optimal pregnancy management.