Evaluation of genetic counselling: recall of information, post-counselling reproduction, and attitude of the counsellees

Of the families who had received genetic counselling between 1972 and 1981, 791 replied to a questionnaire which covered recall of information, post-counselling reproduction and attitudes towards counselling and prenatal diagnosis. Eighty percent had adequate knowledge of mode of inheritance and 74% of recurrence risk. Knowledge of mode of inheritance was poorest in multifactorial transmission (63%) and knowledge of recurrence risk in X-chromosomal disorders (61%). Forty-five per cent of the families had started a pregnancy after the counselling. 25%). Early lethality of the disorder and feasibility of a prenatal study contributed to positive reproductive decisions. Nine per cent of the children born after the counselling were affected by the disorder in question. The observed risks tended to match well with the expected ones. Sixty-two per cent of the respondents felt that the counselling had had a great or moderate impact on their reproductive plans. Forty-two per cent expressed a wish to hear the counsellor's opinion in addition to the facts. This was more common when the disorder was severe. Although most couples (53%) wished to have a prenatal study, if feasible, and abort an affected foetus, 16% were against abortion in such a case and 31% wished to have the study but were ambiguous about an abortion.     

Reproductive drive and genetic counselling

A proper reproductive decision must take the intensity of the reproductive drive into account. Algebraic argumentation clearly shows that binary transposition of the odds and reproductive roulette are often inevitable, especially if the reproductive drive is not duly considered during the counselling process.     

Peutz-Jeghers syndrome and family planning: the attitude towards prenatal diagnosis and pre-implantation genetic diagnosis

Peutz-Jeghers syndrome (PJS) is a hereditary disorder caused by LKB1 gene mutations, and is associated with considerable morbidity and decreased life expectancy. This study was conducted to assess the attitude of PJS patients towards family planning, prenatal diagnosis (PND) and pregnancy termination, and pre-implantation genetic diagnosis (PGD). In a cross-sectional study, 61 adult PJS patients were asked to complete a questionnaire concerning genetic testing, family planning, PND and PGD. The questionnaire was completed by 52 patients (85% response rate, 44% males) with a median age of 44 (range 18-74) years. A total of 37 (71%) respondents had undergone genetic testing. In all, 24 respondents (46%, 75% males) had children. A total of 15 (29%) respondents reported that their diagnosis of PJS had influenced their decisions regarding family planning, including 10 patients (19%, 9/10 females) who did not want to have children because of their disease. Termination of pregnancy after PND in case of a foetus with PJS was considered 'acceptable' for 15% of the respondents, whereas 52% considered PGD acceptable. In conclusion, the diagnosis of PJS influences the decisions regarding family planning in one third of PJS patients, especially in women. Most patients have a negative attitude towards pregnancy termination after PND, while PGD in case of PJS is judged more acceptable. These results emphasise the importance of discussing aspects regarding family planning with PJS patients, including PND and PGD.     

Reproductive genetic counselling in non-mosaic 47,XXY patients: implications for preimplantation or prenatal diagnosis: Case report and review

With an incidence of approximately 1 in 500 male newborns, the 47,XXY genotype is one the most common sex chromosome anomalies. It is also the most frequent genetic cause of human infertility. Some non-mosaic 47,XXY patients have sperm production which allows infertility treatment to be offered by ICSI. Therefore, the risk of transmitting a chromosome anomaly to the next generation is an important problem in reproductive genetic counselling of these patients. Here, we report on a twin pregnancy where two karyotypically normal neonates 46,XX and 46,XY were born after the use of ICSI in assisted reproduction of a patient with a non-mosaic 47,XXY syndrome. To date, only 38 evolving pregnancies including the present cases, have been reported after ICSI using sperm from non-mosaic 47,XXY patients. Although these data are scarce, they suggest that the risk of chromosome anomaly in the offspring of these patients is low; hence, their reproductive genetic counselling can be reassuring, and management of the pregnancy can proceed with caution.     

A child with cystic fibrosis: II. Subsequent family planning decisions, reproduction and use of prenatal diagnosis

In 1984, we interviewed 105 Belgian families with a Cystic Fibrosis (CF) child in order to assess the impact of the birth of their CF-child on subsequent family planning and to evaluate their attitudes towards prenatal diagnosis. Three years later, in 1987, they received a mailed questionnaire for an updating of the reproduction data and to assess their knowledge and intentions with regard to the new possibilities of DNA diagnosis. The birth of a CF-child had a major impact upon subsequent family planning. This effect was found both in the reproductive plans reported by the parents and in the occurrence of pregnancies during the follow-up interval. This effect can be attributed mostly to the recurrence risk and consists of postponing pregnancies as well as of deciding against further offspring. If the CF-child was the firstborn, the chance of having another child was greater than if there was already a healthy child before the birth of the CF-child. Nevertheless, only 47% of the families in which the CF-child was the firstborn, and who could be followed for an average period of 7 years, had another pregnancy. A large majority of families intended to use prenatal diagnosis should a pregnancy occur. In half of the pregnancies that occurred between 1984 and 1987, a prenatal diagnosis was performed. On the other hand, there is less consensus about pregnancy interruption should prenatal diagnosis reveal an affected fetus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors influencing whether or not couples seek genetic counselling: an explorative study in a paediatric surgical unit

To investigate the factors influencing whether or not couples seek genetic counselling, the parents of 37 children with a major congenital anomaly were interviewed at home. All the children had been admitted to the Intensive Care Unit (ICU) of the Department of Paediatric Surgery. After physical examination of the child, the consultant clinical geneticist stated that genetic counselling was indicated for the parents. Whether they sought genetic counselling was left to the parents to decide. Eighteen of the 37 parents had sought genetic counselling. Assessment of the joint influence of a number of factors revealed that two factors were separately paramount in distinguishing between couples who did seek genetic counselling and those who did not: whether parents considered genetic counselling useful in their case shortly after the birth of their affected child, and whether the couple was clearly and correctly informed about the indication for genetic counselling. The intention to have a subsequent pregnancy was not associated with whether or not couples sought genetic counselling. Loss of information was observed: 1/3 of the referrals for genetic counselling mentioned on the written consultation forms were not stated in the discharge letters. This loss of information could have been reduced by a) routinely including the indication for genetic counselling in the discharge letter and b) appointing a coordinating physician to ensure that the parents were informed clearly about the availability of genetic counselling. Resistance to genetic counselling needs to be respected by the physician. Exploring its background might help to reduce this resistance.     

Application of SNP array for rapid prenatal diagnosis: implementation, genetic counselling and diagnostic flow

We report on the validation and implementation of the HumanCytoSNP-12 array (Illumina) (HCS) in prenatal diagnosis. In total, 64 samples were used to validate the Illumina platform (20 with a known (sub) microscopic chromosome abnormality, 5 with known maternal cell contamination (MCC) and 39 normal control samples). There were no false-positive or false-negative results. In addition to the diagnostic possibilities of arrayCGH, the HCS allows detection of regions of homozygosity (ROH), triploidy and helps recognising MCC. Moreover, in two cases of MCC, a deletion was correctly detected. Furthermore we found out that only about 50 ng of DNA is required, which allows a reporting time of only 3 days. We also present a prospective pilot study of 61 fetuses with ultrasound abnormalities and a normal karyotype tested with HCS. In 4 out of 61 (6.5%) fetuses, a clinically relevant abnormality was detected. We designed and present pre-test genetic counselling information on categories of possible test outcomes. On the basis of this information, about 90% of the parents chose to be informed about adverse health outcomes of their future child at infancy and childhood, and 55% also about outcomes at an adult stage. The latter issue regarding the right of the future child itself to decide whether or not to know this information needs to be addressed.     

Intrafamilial variability in the clinical expression of familial hypercholesterolemia: importance of risk factor determination for genetic counselling

Kotze MJ, Davis HJ, Bissbort S, Langenhoven E, Brusnicky J, Oosthuizen CJJ. Intrafamilial variability in the clinical expression of familial hypercholesterolemia: importance of risk factor determination for genetic counselling.
Clin Genet 1993: 43: 295–299. © Munksgaard, 1993
A specific mutation in the low-density lipoprotein receptor (LDLR) gene causes familial hypercholesterolemia (FH) in about 60% of Afrikaner FH heterozygotes. Molecular diagnosis of this so-called FH Afrikaner-1 mutation was performed in a family with the disease. One individual did not develop coronary heart disease (CHD) by age 84, despite having the FH Afrikaner-1 mutation, while his son who inherited the same gene, developed CHD before age 50 and had to undergo bypass surgery. All the sibs in the third generation inherited the defective LDLR gene allele. This variation in clinical presentation creates a counselling dilemma. It also raises questions about the effect of diet and life style, and the possibility of other genes either contributing to the severity of the disease, or protecting against high lipid levels in plasma. An investigation of the influence of selected factors on the clinical expression of the FH Afrikaner-1 mutation in this family indicated that it was especially the elevated apolipoprotein (a) levels, in addition to low levels of high density lipoprotein cholesterol and raised triglyceride and apolipoprotein B levels, that were associated with a greater risk of developing CHD. These findings are thus in accordance with the view that the severity of CHD in FH patients is not only determined by the nature of the gene defect, but is also influenced by other risk factors.     

Reproductive decisions of parents of children with metabolic disorders

The Interaction Model of Client Health Behavior (IMCHB) served as a guide for variable selection and instrument development for telephone interviews with 230 parents of children with metabolic disorders. Sociodemographic, psycho-affective and client-professional interaction variables were examined in relation to three outcomes: (1) receptivity to future prenatal diagnosis (56% were receptive); (2) likelihood of terminating an affected pregnancy (10% would); and (3) whether or not the parent had taken measures to prevent another affected pregnancy (41% had). All three outcomes were significantly correlated with higher scores on the Parent Stress Index, lower scores on the Vineland Adaptive Behavior Scales, fewer persons in the parent's social support network, greater worry about the living child's future and greater perceived difficulty meeting the child's extra care needs. A regression model constructed to explain taking measures to prevent a future affected pregnancy illustrated the usefulness of the IMCHB in research that involves multiple interacting variables on health outcomes. Few of the parents (7.4%) reported an interaction with a genetic counsellor, highlighting the need for practitioners from multiple disciplines to be adequately educated in principles of genetics, especially the psychological and affective aspects of counselling.     

Attitudes toward genetic testing in childhood and reproductive decision-making for familial adenomatous polyposis

Childhood DNA testing, prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) are available for familial adenomatous polyposis (FAP). However, the use of PND and PGD is controversial. The purpose of this study was to investigate attitudes toward, and experiences with, childhood DNA testing, PND and PGD among members of families at high risk for FAP. In this nationwide, cross-sectional study, questionnaires were sent to individuals from families at high risk for FAP assessing attitudes toward and experiences with childhood testing, PND and PGD, as well as several sociodemographic, clinical and psychosocial variables. Of the individuals from FAP families invited to participate in the study, 525 members participated (response rate=64%). Most parents who had children who were minors (n=93) (82%) were satisfied with the DNA testing procedure. One-third of all individuals wanted DNA testing for their children before age 12. Forty percent of FAP patients indicated that the disease influenced their desire to have children. Only 15% considered termination of pregnancy for FAP acceptable. Approximately 30% of individuals with a FAP diagnosis and their partners considered PND and PGD as acceptable for themselves. A positive attitude was associated with higher levels of guilt and a positive attitude toward termination of pregnancy. Importantly, of those with FAP at childbearing age, 84% had had no previous information at all about either PND or PGD. Future efforts should be aimed at educating FAP family members about reproductive options, allowing them to make an informed choice about family planning. Routine discussion of all reproductive options with a medical specialist should be encouraged.     

Reproductive decisions of men with microdeletions of the Y chromosome: the role of genetic counselling.

Couples dealing with microdeletions of the Y chromosome have to make decisions about their reproductive future. Do they opt for intracytoplasmic sperm injection (ICSI), artificial insemination with donor insemination (AID) or no treatment? We analysed this decision in 28 couples and investigated the role of the counsellor and the counselling process on the final decision of the couple. Ten counsellors from six fertility clinics in The Netherlands and Belgium were interviewed about their genetic counselling of couples dealing with microdeletions. The answers to the questionnaire were converted to 11 dichotomous variables. Of the 1627 tested men in the six centres, 37 (2.3%) had a microdeletion in the AZFc region, a subregion of the AZF region on the Y chromosome important for normal spermatogenesis. The decisions of 28 of them could be analysed. Most couples chose ICSI (79%). The remaining couples chose donor insemination (7%) or refrained from treatment (14%). Several variables, including the counselling procedure, the counsellor and the available treatments in the fertility centre, influenced the decision of the couple. In conclusion, most couples dealing with microdeletions in the AZF region choose ICSI. Several aspects of the process of genetic counselling appear to be related to the final decision.     

Reproductive behavior of individuals with increased risk of having a child with retinoblastoma

To investigate reproductive behavior of individuals at increased risk of having a child with retinoblastoma (Rb), we conducted a cross-sectional questionnaire survey among 118 counselees visiting the Clinical Genetics Department of the National Rb Center in the Netherlands. The recurrence risk for counselees ranged from <1% to 50%. The response rate was 69%. Of 43 respondents considering having children after becoming aware of their increased risk, Rb influenced reproductive behavior for 25 (58%), of whom 14 had a recurrence risk <3%. Twenty of these 25 decided against having more children and 5 used prenatal diagnosis. Eighteen of the 43 respondents did not use any of the alternative reproductive options and had children (or more children), although half indicated having had doubts about their decisions. Multiple logistic regression showed that only perceived risk (p = 0.003) was significantly associated with Rb influencing reproductive behavior. Of 17 respondents planning children (or more children), 11 (65%) considered using one of the alternative reproductive options. We conclude that reproductive behavior is greatly influenced by Rb and that perceived risk, not objective risk, is the most important factor of influence. It is important to offer individuals at increased risk continued access to genetic counseling, even when this risk is small.     

Cerebral cavernous malformations: from molecular pathogenesis to genetic counselling and clinical management

Cerebral cavernous (or capillary-venous) malformations (CCM) have a prevalence of about 0.1-0.5% in the general population. Genes mutated in CCM encode proteins that modulate junction formation between vascular endothelial cells. Mutations lead to the development of abnormal vascular structures.In this article, we review the clinical features, molecular and genetic basis of the disease, and management.     

Hemophilia A and B — two years ex-perience of genetic counselling and prenatal diagnosis

Haemophilia A . Thirty-one pregnant women, obligate or probable carriers of haemophilia A, requested prenatal diagnosis if sex determination showed the foetus to be a male. In 11 of the 31 cases the foetuses were females; in two, the genetic variant of the disease rendered prenatal diagnosis impossible; and in two, the mother aborted spontaneously. From the remaining 16 male foetuses, blood samples were obtained in uteri in the 17th to 20th week of gestation. Examination of the samples showed that 11 of the foetuses were unaffected and five affected. Haemophilia B . Three carriers of haemophilia B had male foetuses. Examination of foetal blood obtained in utero showed that these three foetuses were affected. Confirmation . All women with an affected foetus requested termination of pregnancy. In one of thecdses of abortion, no blood was obtained for confirmative examination. In the remaining cases, the prenatal prediction was confirmed in the abortus or in the child after birth; three women are still pregnant.     

Counselling under genetic heterogeneity: a practical approach

Hereditary diseases due to mutation at different gene loci may be indistinguishable phenotypically. In these situations genetic risk predictions using polymorphic markers may be hampered if an individual family is not sufficiently informative to permit it to be assigned to one or the other linkage group. To provide the most usefull estimates of risk, the probability of linkage to a particular chromosome region should be determined prior to calculating risk estimates using the marker system. The probability can be calculated directly using the lod score generated for the family. The individual carrier risk is then the average of the carrier risks determined for linkage to different genetic loci, weighted by the probability of linkage to each group. Several examples are provided.     

Counselling following diagnosis of a fetal abnormality: Comparison of different clinical specialists in Mexico

Most geneticists agree that counselling should be nondirective, and studies report that genetic counselling by geneticists is performed largely in a neutral style. However, couples at risk of having a child with a genetic condition may seek the advice of other physicians. The purpose of the present study was to describe the answers of four groups of specialists from Mexico City (internists, pediatricians, obstetricians, and neurologists) regarding how they would counsel a couple when prenatal diagnosis has shown that a fetus is affected by one of 17 different genetic disorders and to analyze the role of several variables in the development of their opinion. Our results show that physicians in these specialties are more likely to counsel directively than neutrally. Other variables did not influence the directiveness. With respect to direction of influence, internists, pediatricians, and neurologists are more likely to counsel terminating affected pregnancies than are obstetricians (P = 0.0002). Similarly, clinicians older than 37 years of age and those reporting that religion is not important to them counsel terminating affected pregnancies (P = 0.005 and P = 0.003, respectively). Physicians' gender and clinical experience with genetic diseases did not show statistically significant differences. Strong consensus among specialists was reached only on terminating pregnancies in anencephaly. A lowered and moderate consensus (51–75% agreement) was reached on continuing pregnancies with cleft lip and plate. A moderate measure of consensus for nondirective counselling was found among obstetricians regarding 14 of the 17 diseases in the study, whereas neurologists expressed a moderate measure of consensus on counselling the termination of pregnancies when the fetus was affected by neurological disorders. Hence, the approach to counselling was related in part to the fetal condition and in part to the clinician's specialty and age and the self-reported importance of religion. The data presented herein may not be representative of all Mexican physicians within the selected specialties; however, it is important to gather their opinions because they are involved in the care and treatment of genetic diseases and may have an important influence on the demand and availability of prenatal diagnosis and abortion. Am. J. Med. Genet. 69:23–28, 1997. © 1997 Wiley-Liss, Inc.     

Autosomal dominant polycystic kidney disease: New information for genetic counselling

We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which PKD1 disease is unlikely. In 2 families in which ADPKD is not coinherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co-inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progresion. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P < 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late. © 1992 Wiley-Liss, Inc.     

A child with cystic fibrosis: I. Parental knowledge about the genetic transmission of CF and about DNA-diagnostic procedures

In 1984, we interviewed 105 Belgian families with a Cystic Fibrosis (CF) child in order to evaluate their knowledge about the genetic aspect of CF. Three years later, in 1987, they received a mailed questionnaire to assess how well they were informed about the new possibilities of DNA diagnosis. In 1984, three out of the four families were aware of their 25% recurrence risk in subsequent pregnancies. The proportion of correct answers rose to 87% in 1987. The risk that relatives may be asymptomatic carriers was less well known. Only 17% knew that the risk that their own brothers and sisters are carriers of the CF-gene was 1 in 2. The probability that their own healthy children would be carriers of the CF-gene was not known at all. Half of the families who returned the questionnaire thought they were well informed about the new possibilities of DNA-analysis for prenatal diagnosis. The limitations of DNA analysis, however, were poorly understood. The information transfer about the genetic transmission of CF and related topics within the family was also investigated.     

Reproductive decision making before and after predictive testing for Huntington's disease: an Australian perspective

A retrospective study examined both pre- and post-result reproductive decision making for 281 people at risk for Huntington's disease aged 18-45 years who had undergone predictive testing in one centre in Australia between 1990 and 2002. Forty-eight per cent of subjects had one or more pre-result pregnancies, and of these, three had prenatal linkage testing. One high-risk (50%) pregnancy was terminated. Four couples chose an alternative reproductive option. Following testing, data were available for 231 subjects, and no significant difference was found between mutation carriers and non-carriers in the occurrence of post-result pregnancies. This contrasts with the finding of a recent European study, although the outcome of the present study may have been influenced by loss of follow-up data for 50 subjects. Five carriers (17%) had a total of six prenatal tests. Four showed a carrier result and these pregnancies were terminated. Two carriers utilized an alternative reproductive option (donor insemination and pre-implantation genetic diagnosis). The results of this study confirm previous findings of a low uptake of prenatal testing and alternative reproductive options by people at risk for Huntington's disease undergoing predictive testing.     

The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing

Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p<0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p<0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counsellees reported a detericration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.