title: Molecular Diagnostic Challenges and Complex Management of Consecutive Twin Pregnancies in a Family with CD40 Ligand Deficiency.
abstract: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency disorder (PID) caused by mutation in the gene encoding the CD40 ligand (CD40L) expressed on activated T cells. Prenatal genotyping in carriers with twin pregnancies is more challenging than in women with singleton pregnancies. In addition, women with twin pregnancies may decide on selective termination for which the risk of loss of the healthy foetus may exceed 7%. We report here on a family affected by XHIGM. Diagnosis of the disease was made in a male patient as late as 33 years of age. After family screening, the sister of the proband conceived male twins in two consecutive pregnancies. In the first pregnancy, one of the male foetuses was hemizygous for the c.521A>G (Q174R) mutation in the CD40L gene. In the second pregnancy, ultrasound scan showed one foetus to have exencephaly and karyotyping revealed this foetus to have trisomy 18. Several options were discussed, but the parents decided on selective termination in both pregnancies. The interventions were successful in both cases, and the mother now has two healthy sons. This report demonstrates the way in which advanced technologies in molecular medicine and obstetric interventions may assist families with decisions about possible selective termination in case of life-threatening molecular or chromosomal disorders. Diagnosis of CD40L deficiency at the age of 33 years in the proband was striking and indicated that PIDs are still neglected as disease entities in the evaluation of patients with recurrent severe infectious diseases.
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: O
authors.initials: O
authors.lastname: Török
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Tóth
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Erdős
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Csorba
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Gyimesi
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Balogh
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Tóth
authors.affiliation: Department of Obstetrics and Gynecology, University of Debrecen, Debrecen, HungaryDepartment of Infectious and Pediatric Immunology, University of Debrecen, Debrecen, HungaryDepartment of Internal Medicine, University of Debrecen, Debrecen, HungaryDepartment of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Maródi
mesh_terms: D000025:Abortion, Eugenic; D000328:Adult; D023201:CD40 Ligand / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics / Q000276:immunology; D057210:Delayed Diagnosis; D005260:Female; D005865:Gestational Age; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D059285:Pregnancy, Twin / Q000235:genetics* / Q000276:immunology; D011296:Prenatal Diagnosis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000073842:Trisomy 18 Syndrome
chemical_list: D023201:CD40 Ligand