Alobar holoprosencephaly, cebocephaly, and micropenis in a Klinefelter fetus of a diabetic mother

ObjectiveCoexistence of Klinefelter syndrome and holoprosencephaly (HPE) is rare. We report alobar HPE, cebocephaly, and micropenis in a Klinefelter fetus of a mother with type 2 diabetes mellitus with obesity and poor metabolic control.Case ReportA 38-year-old woman was referred for therapy of type 2 diabetes mellitus with poor glycemic control at 24 weeks of gestation. On examination, she had a body height of 162 cm and a body weight of 105 kg. She had been treated with oral medication for diabetes mellitus for 4 years with poor maternal metabolic control. She had prominent glucosuria and glycemia. Her hemoglobin A1c was 7.5% (normal range: 3.4–6.1%), and the fasting glucose level was 141 mg/mL (normal range: 70–99 mg/mL) during this visit. Her husband was 46 years old. Prenatal ultrasound revealed a singleton fetus with fetal biometry equivalent to 24 weeks, alobar HPE, cebocephaly, and micropenis. As a result of poor maternal heath and fetal anomaly, the parents elected to terminate the pregnancy, and a 986-g male fetus was delivered with hypotelorism, HPE, cebocephaly, micropenis, and cryptorchidism. Cytogenetic analysis of the cord blood revealed a karyotype of 47,XXY. The parental karyotypes were normal. Polymorphic DNA analysis revealed a paternal origin of the extra X chromosome. Molecular analysis of the HPE genes of SHH, ZIC2, SIX3, and TGIF revealed no mutations.ConclusionPrenatal diagnosis of HPE should include a biochemical examination to identify metabolic factors such as maternal diabetes, and preventive management should be considered in subsequent pregnancies to achieve good control of maternal diabetes.