Knowledge and perceived risks in couples undergoing genetic testing after recurrent miscarriage or for poor semen quality.

Couples with recurrent miscarriage (RM) and men with poor semen quality may undergo genetic testing as part of the diagnostic work-up. This study explored their knowledge and perception of genetic testing, evaluated psychological wellbeing and identified associated variables. A prospective questionnaire study was conducted in seven clinical genetics centres and referring gynaecological departments in couples with RM or poor semen quality. Questionnaires were completed before disclosure of genetic test results. Main outcome measures were knowledge, perceived risk, anxiety and depression. Of 439 participants, 256 were not aware genetic testing was part of the diagnostic work-up. One-third (36% RM, 33% poor semen quality) indicated they had not received information about the genetic test from their doctor. Perceived risk of receiving an abnormal genetic test result was higher than objective risk. Anxiety was highly correlated with perceived risk. Women with RM were more anxious than women in the poor semen quality group or men (P<0.01). These couples undergoing genetic testing have a suboptimal understanding of the nature of testing, overestimate the risks of receiving an abnormal result and some show high levels of anxiety. The results of this study can be used to improve patient counselling before genetic testing.

Changes in yearly birth prevalence rates of children with Down syndrome in the period 1986-2007 in The Netherlands.

BACKGROUND: The Netherlands are lacking reliable national empirical data in relation to the development of birth prevalence of Down syndrome. Our study aims at assessing valid national live birth prevalence rates for the period 1986-2007. METHOD: On the basis of the annual child/adult ratio of Down syndrome diagnoses in five out of the eight Dutch cytogenetic centres, the national annual figures of the National Cytogenetic Network on total numbers of postnatal Down syndrome diagnoses were transformed into national figures on total numbers of postnatal Down syndrome diagnoses in newborn children only. In combination with the national annual data of the Working Group for Prenatal Diagnostics and Therapeutics on numbers of Down syndrome pregnancies not aborted after diagnosis, national figures on birth prevalence were constructed. RESULTS: For the period 1986-2007, results based on the data of the cytogenetic centres are almost similar to the theory-based model data of de Graaf et al., with a small discrepancy of approximately 4%. Down syndrome birth prevalence in the Netherlands shows an upward trend from around 11 per 10,000 births in the early 1990s to around 14 per 10,000 births nowadays. CONCLUSION: In spite of expansion of antenatal screening in the Netherlands, Down syndrome live birth prevalence has risen in the last two decades as a result of rising maternal age. This increase in Down syndrome birth prevalence is in contrast to studies from other European countries.

[Risk factors for structural chromosomal abnormality in > or = 2 miscarriages, as an instrument for selective karyotyping]. / Risicofactoren voor structurele chromosoomafwijking bij > or = 2 miskramen als instrument voor selectieve karyotypering.

OBJECTIVE: To identify additional risk factors and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages. DESIGN: Nested case-control study. METHOD: In 6 centres for clinical genetics in the Netherlands, data were collected from couples referred for karyotyping after 2 2 miscarriages from 1992-2000. Factors influencing the probability of carrier status were examined. The corresponding probability of carrier status was calculated for the various combinations of these factors. RESULTS: In total 279 carrier couples and 428 non-carrier couples were included. 4 independent factors influencing the probability of carrier status were identified: a younger maternal age at the time of second miscarriage, a history of > or = 3 miscarriages, a history of > 2 miscarriages in a brother or sister of either partner, and a history of> 2 miscarriages in parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages, varied between 0.5-10.2%. In 18% of couples included, the risk was found to be so low (< 2.2%), that in couples with comparable risk factors, it may not be necessary to perform karyotyping. CONCLUSION: This study demonstrated that the probability of carrier status in couples with > or = 2 miscarriages is modified by additional factors. Selective chromosome analysis would result in a more effective referral policy and therefore decrease the number of chromosome analyses and lower the costs.

Subfertile men with constitutive chromosome abnormalities do not necessarily refrain from intracytoplasmic sperm injection treatment: a follow-up study on 75 Dutch patients.

A follow-up study was performed to investigate the impact of the detection of a chromosome abnormality in infertile men who are candidates for intracytoplasmic sperm injection (ICSI) treatment. In this collaborative study between clinical genetics centres and fertility clinics in the Netherlands, 75 ICSI couples of which the male partners had a chromosome abnormality were included. All couples were extensively counselled on the risk of having a chromosomally unbalanced child. Forty-two out of 75 couples chose to proceed with the ICSI treatment. So far, treatment has resulted in a pregnancy in 11 cases. Four of them opted to have invasive prenatal diagnosis. Despite the genetic risks related to a chromosome abnormality in infertile men, a small majority (56%) of the couples did not refrain from the ICSI treatment.

Chromosome studies in 1792 males prior to intra-cytoplasmic sperm injection: the Dutch experience.

The chance of a male with severe oligozoospermia or azoospermia achieving a pregnancy has undergone a revolutionary increase with the introduction of the intracytoplasmic sperm injection technique (ICSI). However, since ICSI circumvents part of the natural sperm selection mechanisms, the possible transmission of genetic defects to the offspring is a major concern. Cytogenetic analysis is a relatively simple technique to identify at least the carriers of a chromosomal aberration before starting the ICSI procedure. In order to assess the frequency of chromosomal aberrations in male ICSI candidates, we have performed a nationwide cytogenetic study. Of the 1792 males examined, 72 (4.0%) revealed a chromosomal aberration, and one individual even had two. Numerical sex chromosomal aberrations and Robertsonian translocations predominated, followed by reciprocal translocations, inversions and supernumerary marker chromosomes. The different implications, in case a chromosomal aberration is encountered prior to ICSI, are discussed.

A case of de novo interstitial deletion of chromosome 5(q33q34).

The present paper describes a girl with a small de novo deletion of chromosome 5(q33q34). Fluorescence in situ hybridisation with locus specific probes was used to define the extent of this deletion. Clinical features in this patient are microcephaly, dysmorphic facial features such as epicanthus, small biparietal distance and retrognathia, four-finger lines on both hands and mild mental retardation.

At least nine cases of trisomy 11q23-->qter in one generation as a result of familial t(11;13) translocation.

Carriers of balanced reciprocal translocations may have a (high) risk for producing liveborn children with an unbalanced karyotype. We report a large family in which a translocation between the long arm of chromosome 11 and the short arm of chromosome 13 is segregating in at least five generations. During the course of our study 15 carriers of the balanced translocation were identified and nine cases of partial trisomy of the long arm of chromosome 11 were detected during pre- and postnatal studies. Several of the patients were thoroughly clinically examined and compared with similar published cases.

Intracranial teratoma with multiple fetuses: pre- and post-natal appearance.

An intracranial teratoma in which six distinct dysmorphic fetuses were included was studied at autopsy. Karyotopic studies showed a normal chromosomal number in the child and the same karyotype in the three tumoral parts were examined. This is the second tumor of this type reported.

A case of de novo interstitial deletion of chromosome 9(p12p13).

The present paper describes a girl with a small de novo deletion of chromosome 9(p12p13). This deletion has not been published previously. The deleted fragment is clearly outside the region involved in the so-called deletion 9p syndrome. The patient had mild dysmorphic features and feeding problems during the first weeks of life, but is now developing well. Because of the lack of severe clinical features in this patient, we speculate that the deletion may be prevalent in other patients who have no clinical indication for chromosome investigation.

Paracentric inversion inv(11)(q21q23) in The Netherlands.

We report the result of investigations from 20 families with 72 carriers of the paracentric inversion inv(11)(q21q23) in the Netherlands. There is no increase in the rate of spontaneous abortions among carriers of the inversion or their partners. Also, so far, there are no children with recombinant chromosomes arising from the inversion. It is doubtful whether prenatal diagnosis would be helpful to carriers of this inversion. The results of the genealogy study and geographical distribution are discussed; it is suggested that all the families have arisen from a single mutation.

Partial duplication 14q/deletion 2q in two sibs due to t(2;14) (q37.1;q31.2) pat.

Two siblings are described with duplication 14q/deletion 2q due to a paternal translocation (2;14) (q37.1;q31.2). The first one, a boy, born at term, lived 14 days. The second one, a female foetus, was born after induced labour when the anomaly was discovered by way of amniocentesis. They both had almost identical phenotypes. From a study of the literature it is inferred that a typical asymmetric head form, low set abnormal ears, micrognathia, long upper lip, rib anomalies, camptodactyly, long fingers and contractures are prominent features of the syndrome.