Pregnancy outcomes in 188 French cases of prenatally diagnosed Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS), a common sex chromosome aneuploidy (47,XXY) is diagnosed prenatally with an incidence of 0.15%. The diagnosis is generally incidental, since there are no typical malformations on ultrasound (US). Once detected, genetic counseling is often difficult and the parents' decision to continue or terminate the pregnancy is greatly dependent on the amount and nature of the information provided. We sought to assess the pregnancy outcomes (i.e. continuation versus termination) and the influence of multidisciplinary centers for prenatal diagnosis on parental decisions in cases of KS. METHODS: From 1985 to 2009, 188 prenatal diagnoses of KS were made by 11 participating laboratories in mainland France. In each case, the karyotype indication, parental ages, year of prenatal testing, sampling procedure, karyotype, associated US findings and outcome were recorded. RESULTS AND CONCLUSIONS: The pregnancy termination rate declined markedly over time, from 46.9% before 1997 to 11.6% thereafter, in line with the introduction of new legislation on prenatal diagnosis for medical reasons and, more specifically, the creation of multidisciplinary prenatal diagnosis centers. However, an additional microdeletion in one KS infant who exhibited echogenic bowel on US was unfortunately diagnosed postnatally. This raises the question as to whether array comparative genomic hybridization should be prenatally advised when US abnormalities are detected, in line with advice for fetuses with a normal karyotype.

[Recourse to amniocentesis after the age of 38. Factors related to access to medical care]. / Recours à l'amniocentèse après 38 ans. Facteurs liés à l'accès aux soins.

Antenatal screening by amniocentesis was not much used in Haute-Normandie (France) in 1981. This study compared 59 women aged 38 and over who did benefit from this test with a control sample of 71 women who delivered in the same region at the same time and who were not screened. The use of the screening was linked to the socio-professional category of the woman, to her professional activity, to her nationality, to where she studied, to her parity, and the quality of her obstetrical care. The information that the women who were screened had about trisomy 21 and its screening was far higher in those who were screened. Regression analysis indicates that there are 3 factors that play an important role: whether the specialist or the general practitioner offered the screening test and the socio-professional category of the woman. Amniocentesis could be used much more efficiently if the population was better informed and if the medical corps made a special effort as well as providing more screening facilities.

[Microdeletion of 22q11 and conotruncal cardiopathies: contribution of prenatal diagnosis]. / Microdélétion 22q11 et cardiopathies conotroncales: apport du diagnostic prénatal.

OBJECTIVE: We report our experience on prenatal diagnosis of 22q11 deletion by fluorescent in situ hybridation (FISH). PATIENTS AND METHODS: From February 1997 to April 1998, prenatal diagnosis of 22q11 deletion was performed in 13 cases of congenital conotruncal heart defects. FISH was carried out using D22S75 DiGeorge's chromosome region probe. RESULTS: Microdeletions of 22q11 were detected in 4 fetuses with tetralogy of Fallot (3 cases) and pulmonary atresia with ventricular septal defect (1 case). Termination of pregnancy was performed in two cases for severe congenital heart defect. A third malformed fetus died immediately after a blood sampling procedure. The last fetus, with a tetralogy of Fallot malformation, was born and underwent corrective cardiac surgery. The dysmorphic features of this fetus was suggestive of DiGeorge's syndrome, and the development status was normal. CONCLUSION: Prenatal detection of 22q11 only played a minor role in the decision to terminate the pregnancy in our study.

Complex chromosomal rearrangement and intracytoplasmic sperm injection: a case report.

Complex chromosomal rearrangements (CCRs) are rare events in human pathology and are usually considered to induce severe reproductive impairment by disturbing the meiotic process and producing unbalanced gametes responsible for high reproductive risk. One-third of all CCRs are familial and tend to implicate fewer breakpoints and fewer chromosomes than de novo cases. CCRs are rarely transmitted through spermatogenesis and are primarily ascertained by male infertility. We report a familial balanced CCR, with seven breakpoints involving three chromosomes, which was detected prenatally in a female fetus conceived after intracytoplasmic sperm injection (ICSI) in a couple initially thought to be a carrier of a paternal reciprocal translocation involving two chromosomal breakpoints. Fluorescent in-situ hybridization (FISH) was used to elucidate the complexity of this CCR. The karyotype of the female CCR carrier was balanced and determined as 46,XX.ish t(1;4)(q42;q32)(WCP1+, D1Z5+, WCP4+, D1S3738-, D4S2930+; WCP4+, D4Z1+, WCP1+, D4S2930-, D1S3738+), ins(1;11)(q41;q23q24)(WCP1+,WCP11+, D11S2071-, MLL+; WCP11+, D11S2071+, WCP1-, MLL-), ins(4;11)(q23;q14q23)(WCP4+,WCP11+; WCP11+,WCP4-). The same balanced CCR was confirmed in her oligozoospermic father. We report, to our knowledge, the first case of ICSI performed in an infertile male with CCR, resulting in a balanced CCR carrier female with a normal clinical follow-up at 4 years of age. This particular case stresses the point of the relevance and feasibility of ICSI procedure in cases of balanced CCRs.

Detection of an Alu insertion in the POMT1 gene from three French Walker Warburg syndrome families.

Walker Warburg syndrome (WWS) is the most severe of a group of multiple congenital disorders known as lissencephaly type II ( LIS Type II) associated with congenital muscular dystrophy and eye abnormalities. The POMT1 gene is the most frequently affected found in 20% of patients with WWS. We describe five fetuses with WWS in three non-related families carrying a same mutation in the POMT1 gene. All fetuses presented with tetra ventricular hydrocephaly, and arachnoidal neuroglial ectopia and cortical dysplasia characteristic of LIS type II. We performed sequencing of the POMT1 gene on fetal DNA. The five fetuses were found to share an insertion of an inversed Alu repeated DNA element within exon 3 of the POMT1 gene, all at the heterozygous state except one at the homozygous state. This mutation was associated with a common transition c.2203 C > T (p.Arg735Cys) in exon 20 on the same allele and similar intragenic haplotype, suggesting that the three families could be related or indicating a possible founder effect in France. Insertions of Alu sequences, which are rarely found in coding regions, have occasionally been reported to cause other genetic diseases. However, this is the first report of a retrotransposon insertion in the POMT1 gene associated with WWS.

[Trisomy 9p by mat. t(2;9)(q36;q31)]. / Trisomie 9p par t(2;9)(q36;q31) mat.

Two sibs are reported with partial trisomy 9, the consequence of a maternal reciprocal translocation.

[Polysyndactyly with complex cardiopathy. Apropos of 3 cases in the same family]. / Polysyndactylie avec cardiopathie complexe. A propos de trois cas dans une même fratrie.

This study deals with a family where three successive children presenting with a complicated polymalformative syndrome, died. The first child, a boy, had atrial and ventricular septal defect. The second and third children, both females, had cardiac abnormalities with a single ventricle with common auriculo-ventricular valve. Each case was associated with low ear insertion and first toe bilateral polysyndactyly. Familial inquiry showed neither consanguinity nor similar cases in relatives and ancestors within three generations. This polymalformative syndrome could be genetically determined.

Fetal adrenal development during the second trimester of gestation.

Four hundred and fifty pairs of adrenals were studied from human fetuses ranging in age from 15 to 27 weeks of gestation (menstrual age). They were collected from spontaneous and medical abortions. The adrenal weight increased from 0.2 to 1.5 g during the second trimester. The left adrenal was significantly heavier than the right for the same gestational age. The length (L1), the height (L2) and the thickness (L3) of the adrenals were measured. The index of length (L1 x L2 x L3) correlated well with the fetal age, except for the Potter Syndrome in which it was decreased. This index could be a useful indicator for ultrasonographic and pathologic studies of the fetal adrenal gland. The cells of the fetal cortex contained lipid droplets during the first weeks of the mid-trimester, and this storage progressively decreased after 20-21 weeks. The fatty transformation that is used as an indicator of the mode of death of stillborn infants cannot be applied to abortions during the second trimester. In a few instances, hypoxia was associated with adrenal hypertrophy.

Collaborative study of mosaic tetrasomy 12p or Pallister-Killian syndrome (nineteen fetuses or children).

The difficulties in the diagnosis of Pallister-Killian syndrome are illustrated in this study of nineteen fetuses and children. Diagnosis based on clinical appearance alone is often difficult due to the broad spectrum of clinical anomalies not specific to this syndrome. Due to mosaicism, it is altogether necessary to examine several tissues for the presence of tetrasomy 12p, including circulating lymphocytes in which mosaicism can be as low as 1-3%, amniocytes, chorionic cells and skin fibro-blasts in which mosaicism ranges from 6-100%. When highly suspected on ultrasound examination, the diagnosis recommends prenatal cytogenetic studies because survivors are severely mentally retarded. All the cases are sporadic with only a single preliminary report of recurrence. The cytogenetic diagnosis is therefore helpful in order to reassure family members in regard to genetic counseling.