Caudal regression syndrome in a fetus of a glucokinase-maturity-onset diabetes of the young pregnancy

Background Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is a form of diabetes caused by heterozygous inactivating mutations in the GCK gene. Affected individuals maintain their fasting glucose levels at a higher set point (5.4-8.3 mmol/l) than the general population. Hyperglycaemia in women with Type 1 or Type 2 diabetes is known to confer increased risk of fetal congenital abnormalities. The association between GCK-MODY and congenital abnormalities, however, remains uncertain. Case report A 35-year-old woman in her third pregnancy was diagnosed with gestational diabetes at 13 weeks' gestation (fasting blood glucose 6.0 mmol/L, 1-h blood glucose 9.2 mmol/l, 2-h blood glucose 7.3 mmol/l). The morphology scan at 19+2 weeks' gestation showed a Type III sacral agenesis. The woman elected to terminate the pregnancy. Her postpartum oral glucose tolerance test was suggestive of GCK-MODY (fasting blood glucose 7.4 mmol/l, 1-h blood glucose 9.3 mmol/l, 2-h blood glucose 7.3 mmol/l). Mutation analysis of the GCK gene identified a novel heterozygous GCK missense mutation, p.V199M, classified as likely pathogenic, providing molecular confirmation of the suspected GCK-MODY diagnosis. Discussion Sacral agenesis is a rare form of sacral abnormality affecting 0.005% to 0.1% of pregnancies. It is a subtype of the caudal regression sequence, a cardinal feature of diabetic embryopathy. This case raises the question as to whether hyperglycaemia in GCK-MODY may increase the risk of fetal caudal regression syndrome as reported in women with pre-existing diabetes mellitus. Improved diagnostic rates of GCK-MODY, and MODY registers that include pregnancy outcomes, are important to further elucidate risk of congenital abnormalities in GCK-MODY.