title: Alobar holoprosencephaly, cebocephaly, and micropenis in a Klinefelter fetus of a diabetic mother.
abstract: OBJECTIVE
  Coexistence 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.
  
  
  METHODS
  A 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.
  
  
  CONCLUSIONS
  Prenatal 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.
authors.affiliation: Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan. cpc_mmh@yahoo.com
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Su
authors.forename: Schu-Rern
authors.initials: SR
authors.lastname: Chern
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Su
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: Wayseen
authors.initials: W
authors.lastname: Wang
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000025:Abortion, Eugenic; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D016142:Holoprosencephaly / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D059785:Karyotype; D007713:Klinefelter Syndrome / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D009765:Obesity / Q000150:complications; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D011296:Prenatal Diagnosis