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

Abstract

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.

Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

“…a 30% risk increase per 1% (11 mmol/mol) increase in HbA 1c above 6.3% (45 mmol/mol), if one refers to data obtained in women with pregestational diabetes ( 2 ). One case of caudal regression syndrome was reported, and the potential benefit of systematic peri-conceptual folic acid supplementation in women with known GCK -MODY has been suggested (as actually recommended in the general population) ( 43 ). A pulmonary valve stenosis was reported in a child born to a GCK -MODY mother, whose early pregnancy HbA 1c was 6.5% (48 mmol/mol) ( 44 ).…”

Maturity-Onset Diabetes of the Young and the Structure of Gestational Diabetes Mellitus

“…Было принято решение о прерывании беременности. Признавая возможность «случайного» развития СКР, авторы отметили, что гипергликемия матери может повышать риски формирования врожденных пороков развития, в том числе СКР [44].…”

Pregnancy in a patient with caudal regression syndrome following continent bladder reconstruction

“…Maternal diabetes mellitus can induce CRS. 1 CRS is complicated with neurodevelopmental disorders of vesico-rectal functions and the lower extremities. Of those, intractable urinary incontinence due to neurogenic intrinsic sphincter deficiency necessitates the life-long use of diapers, and, thus, a woman with CRS may have psychosocial problems in sexual intercourse ability.…”

“…Caudal regression syndrome (CRS) is a rare congenital malformation, which is characterized by abnormal development of the lower end of the spine. Maternal diabetes mellitus can induce CRS 1 . CRS is complicated with neurodevelopmental disorders of vesico‐rectal functions and the lower extremities.…”