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.     

Mexican geneticists’ views of ethical issues in genetics testing and screening. Are eugenic principles involved?

Herein we discuss Mexican geneticists' views of ethical issues in genetic testing and screening, analyzing whether eugenic principles are involved in this activity. The information was obtained from a comprehensive survey on genetics, ethics, and society organized by Wertz and Fletcher in 1993, in which 37 nations participated. The responses to 21 questions from 64 out of 89 (72%) geneticists invited to participate are analyzed in this paper. The questions were practically the same as those answered recently by a group of Chinese geneticists (Mao X. Chinese geneticists' views of ethical issues in genetic testing and screening: evidence for eugenics in China. Am J Hum Genet 1998: 63: 688-695), who work in a country where the furtherance of eugenic principles is considered to be the goal of human genetics. We concluded that although there are many similarities in the answers from both countries, this is not indicative of Mexican geneticists pursuing eugenic goals because: a) there is no coercion involved; and b) there is no intention of improving the gene pool.     

Postmortem chorionic villus sampling: correlation of cytogenetic and ultrasound findings

We performed chorionic villus samplings (CVS) in 795 cases in the first trimester during a 13-month period. Of these 35 were found to have a blighted ovum or missed abortion prior to the procedure. Nineteen women consented to have CVS. Ultrasonographic and cytogenetic findings in these 19 pregnancies were correlated. Expected gestational age was determined by last menstrual period. Observed gestational age was determined by crown rump length (CRL) (12 pregnancies) or gestational sac (GS) (7 pregnancies without fetal pole). The differences in days between the estimated and observed gestational ages was determined for each pregnancy. In all 19 CVS samples cytogenetic diagnosis documented aneuploidy. Ten cases had chromosome abnormalities virtually always lethal in the embryonic period (group I). Nine pregnancies had defects with moderate potential for fetal viability (group II). Gestations with low viability potential (group I) had estimated minus observed gestational age discrepancies (23.4 +/- 8.3 days) significantly greater than gestations with moderate viability potential (group II) (8.9 +/- 4.3 days) (P less than .001). The absence of a fetal pole was more common in group I. CVS in pregnancies with missed abortion or blighted ovum is feasible and has a high likelihood of documenting aneuploidy. Furthermore, the more severe the anomaly the more likely there will be very early fetal demise or intrauterine growth retardation.     

Counselling following diagnosis of a fetal abnormality: the differing approaches of obstetricians, clinical geneticists, and genetic nurses.

Women receiving a positive diagnosis of an abnormality during pregnancy may be counselled about a termination by one of several types of health professionals including obstetricians, geneticists, and genetic nurses. There is anecdotal evidence to suggest that these groups differ in both their approaches to counselling and their attitudes towards abnormality. The aim of the current study is to document how genetic nurses, geneticists, and obstetricians describe their own counselling of women following the diagnosis of specific fetal abnormalities. Obstetricians reported counselling in a significantly more directive fashion than did geneticists, who in turn reported counselling in a more directive way than did genetic nurses. The extent to which the groups differed in their reported approaches varied across conditions. The most marked difference was evident for Down's syndrome: 94% of genetic nurses, 57% of geneticists, and 32% of obstetricians reported counselling non-directively. Future research needs to focus on what these different groups see as the objectives of counselling in this situation, how they actually counsel, and with what effects.     

Bearing crosses: A historiography of genetics and embryology

As we construct the fusion of medical embryology and medical genetics, it is important to be aware of how the history of genetics has been written to exclude embryology. This article looks at the rhetoric of genetics and how that rhetoric fits a paradigm of supersessionism. Supersessionism is often seen in the history of religion when one sect claims superiority to the original sect from whence it emerged. Such supersessionism portrays embryology as a failed research program, one that genetics now has saved. In some instances, biblical references have alluded to the failed nature of embryology. Although this article does not criticize the data of genetics, it takes issue with the historiography used by geneticists and seeks to show that the mergers between genetics and embryology are those between two equal partners and not between an inferior and superior member. Am. J. Med. Genet. 76:168–182, 1998. © 1998 Wiley-Liss, Inc.     

Genetic aspects of population policy.

Every science begins in folklore and matures as it reacts against dogma and myth. Astronomy developed in the Neolithic, but it did not outgrow astrology until the sixteenth century. Chemistry discarded alchemy at about the same time. On the contrary, the short history of genetics has been concurrent with the pseudo-science of eugenics, which, at times, has been widely accepted and incorporated in population policy and directive genetic counselling, with rare opposition by geneticists. Societal pressures are likely to increase with the power of genetic technology, the fear it generates and the perception that population growth threatens human welfare. Without a pertinent ethical code, geneticists are vulnerable to both temptation and opprobrium. The intrusion of eugenics into genetic counselling has been a recent source of concern to societies and congresses of genetics. This review traces the causes of this concern and the manner of its expression in the absence of an international voice for genetics that could address ethical and other common interests.     

Noncompaction of the ventricular myocardium in Melnick-Needles syndrome

A 4-year-old asymptomatic boy was referred for evaluation after being diagnosed with Melnick-Needles syndrome. Echocardiography demonstrated noncompaction of the left ventricular myocardium as an isolated cardiac finding. Though other structural cardiac defects were reported previously in this syndrome, this is the first report of this rare cardiac anomaly in this likewise rare syndrome. We postulate that this occurrence represents a primary disorder of early fetal development. Patients with Melnick-Needles syndrome should be evaluated for noncompaction of the ventricular myocardium and its potential cardiovascular dysfunction. Am. J. Med. Genet. 71:72–75, 1997. © 1997 Wiley-Liss, Inc.     

Choanal atresia and hypothelia following methimazole exposure in utero: A second report

We report on a 3-year-old boy with bilateral choanal atresia, hypoplastic nipples, and developmental delay who had been exposed to carbimazole in utero because of maternal Graves disease. His combination of abnormalities and facial appearance strongly resembles that of a previously reported child exposed to methimazole (which is the active metabolite of carbimazole) in utero. We suggest that this represents a rare but distinct syndrome of methimazole teratogenicity, probably related to first-trimester exposure. Recognition of such teratogenic effects is clearly important for genetic counselling and for management of subsequent pregnancies. Am. J. Med. Genet. 75:220–222, 1998. © 1998 Wiley-Liss, Inc.     

Segregation analysis of Parkinson disease

Parkinson disease (PD) is a prevalent movement disorder of unknown cause whose incidence rises with increasing age. Nearly 20% of PD is familial, a small subset of which exhibits autosomal dominant transmission. However, in most families, the inheritance is not clear. To determine the most likely mode of inheritance of PD, we performed complex segregation analyses using kindreds of 136 PD patients randomly ascertained from a clinic population. The hypotheses of a nontransmissible environmental factor, no major gene or type (sporadic), and all Mendelian inheritance (dominant, recessive, additive, decreasing) were rejected (P <0.001). Familial clustering of PD in this data set is best explained by a rare familial factor which a) is transmitted in a non-Mendelian fashion, and b) influences the age at onset of PD. If confirmed, our results have immediate implications in gene-mapping studies which often search for genes that behave in a Mendelian fashion that affect susceptibility rather than age at onset and long term implications in understanding the pathogenesis of PD. Am. J. Med. Genet. 80:410–417, 1998. © 1998 Wiley-Liss, Inc.     

Spontaneous abortion in multiple pregnancy: focus on fetal pathology

Multiple pregnancy with its wide array of medical consequences poses an important condition during pregnancy. We performed perinatal autopsy in 49 cases of spontaneous abortion resulting from multiple pregnancies during the study period. Twenty-seven of the 44 twin pregnancies ending in miscarriage were conceived naturally, whereas 17 were conceived through assisted reproductive techniques. Each of the 5 triplet pregnancies ending in miscarriage was conceived through assisted reproductive techniques. There was a positive history of miscarriage in 22.4% of the cases. Monochorial placentation occurred more commonly in multiple pregnancies terminating with miscarriage than in multiple pregnancies without miscarriage. A fetal congenital malformation was found in 8 cases. Three of these cases were conceived through assisted reproductive techniques, and 5 were conceived naturally. Miscarriage was due to intrauterine infection in 36% of the cases. Our study confirms that spontaneous abortion is more common in multiple than in singleton pregnancies. Monochorial placentation predicted a higher fetal morbidity and mortality. In pregnancies where all fetuses were of male gender, miscarriage was more common than in pregnancies where all fetuses were female. Assisted reproductive techniques do not predispose to the development of fetal malformations.     

Chromosome 22 workshop report

The chromosome 22 workshop took place at the Sixth World Congress on Psychiatric Genetics from October 6th–10th, 1998 in Bonn, Germany. Aim of the workshop was to summarize the findings in psychiatric genetics on chromosome 22. Four reports concerning a susceptibility locus for schizophrenia and one report on bipolar disorder were given. A potential locus for nocturnal enuresis has been suggested to reside on chromosome 22. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:276–278, 1999. © 1999 Wiley-Liss, Inc.     

Predictive value of the triple screening test for the phenotype of Down syndrome

Maternal serum alpha-fetoprotein (MS-AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in the second trimester (“triple” test) and combined with maternal age to evaluate risk for fetal Down syndrome. Triple test results and clinical findings were retrospectively reviewed for 30 newborns with Down syndrome to determine whether analyte values or second trimester risks for Down syndrome were more extreme in affected pregnancies where cardiac or other severe congenital malformations were present compared to those cases where major anatomical abnormalities were absent. Mean MS-AFP, uE3, maternal age, and second trimester Down syndrome risk were all similar in the two groups of pregnancies. However, hCG concentrations did appear to be higher in the group of Down syndrome pregnancies with anatomical anomalies (mean 1.74 MoM versus 1.19 MoM) (P < 0.05). Overall, there was no significant difference in the incidence of major anomalies in patients with screen-positive test results versus those cases that were not identified by the triple test. Prenatal counseling should therefore reflect the general expectations of the Down syndrome phenotype that have been established from live-born infants with this disorder. Am. J. Med. Genet. 85:123–126, 1999. © 1999 Wiley-Liss, Inc.     

Permanent Committee of the International Congresses of Human Genetics

For over three decades, the Permanent Committee of the International Congresses of Human Genetics has served the purpose of selecting a host and site for the quadrennial Congress, which is due next in 2001. The Committee has statutes and consists of one voting representative from 38 nations and other ex officio members, much like the General Assembly of the United Nations. It meets twice during each International Congress, otherwise conducting its business by mail and telecommunication. Its structure could be the beginnings of a truly global democratic body of human geneticists to address other issues and to serve other purposes, as human genetics becomes increasingly international, as inevitably it must. Am. J. Med. Genet. 79:79–81, 1998. © 1998 Wiley-Liss, Inc.     

Risk of spontaneous abortion in singleton and twin pregnancies after IVF/ICSI

BACKGROUND: The risk of spontaneous first trimester abortion is estimated to be between 10 and 20%. Although it is common knowledge that the incidence of abortion decreases as pregnancy progresses, exact data in relation to the duration of pregnancy are scarce. METHODS: We reviewed 1597 clinical IVF/ICSI pregnancies with known outcome and tabulated the number of miscarriages or fetal demise per intervals of 2 weeks. We furthermore compared the outcome in terms of fetal survival of 1200 singleton pregnancies with that of 397 twin pregnancies. RESULTS: The overall incidence of non-ongoing singleton pregnancies was 21.7%. Fetal death, after positive heart activity had been recorded, occurred in 12.2% of singleton pregnancies. The overall incidence of spontaneous abortion in twin pregnancies was 17.1% (12.1% vanishing twins and 5.0% complete miscarriages). The incidence of miscarriage in the twin pregnancies, expressed per gestational sac, was 11.1%. Once fetal heart activity was present, the risk of abortion (per gestational sac) was 7.3%, which is significantly lower than that in singleton pregnancies. CONCLUSIONS: Our data give an estimate of the probability of miscarriage or fetal demise at any given period of the first trimester both for singleton and twin pregnancies. Twin pregnancies after IVF have a better potential for survival than singleton pregnancies.     

Early transvaginal ultrasound following an accurately dated pregnancy: the importance of finding a yolk sac or fetal heart motion

Our goals were to determine the prognostic value of a yolk sac or fetal heart motion seen during an early accurately dated transvaginal ultrasound (TVU). We reviewed 225 consecutive pregnancies for fetal heart motion data. Furthermore, 63 pregnancies following in-vitro fertilization were reviewed for yolk sac information. The TVU was performed between 5 and 6 weeks following presumed conception (heart motion data) and between 22 and 32 days following in-vitro fertilization (yolk sac data). Pregnancies were followed until an ongoing pregnancy or spontaneous abortion was documented. The presence of a yolk sac between 22 and 32 days from fertilization was associated with the development of fetal heart motion in 94% of cases. The absence of the yolk sac by 32 days after fertilization was always associated with a poor outcome. In women < 36 years of age, the presence of fetal heart motion was associated with a spontaneous abortion in only 4.5% of the cases. However, the incidence of spontaneous abortion following fetal heart motion increased to 10% in women 36-39 years and 29% in women > or = 40 years of age. The presence of heart motion should not be considered a reassuring sign in the older woman. These data have implications regarding early embryology and the counselling of infertility patients.      

Mild autosomal dominant hypophosphatasia: In utero presentation in two families

We describe four pregnancies in two families in which mild hypophosphatasia, apparently transmitted as an autosomal dominant trait, manifested in utero as severe long bone bowing. Postnatally, there was spontaneous improvement of the skeletal defects. Recognition of this presentation for hypophosphatasia by family investigation and assessment of the fetal skeleton for degree of ossification and chest size using ultrasonography is important. The prognosis for this condition is considerably better than for more severe forms of hypophosphatasia and for many other disorders that cause skeletal defects with long bone bowing in utero. Am. J. Med. Genet. 86:410–415, 1999. © 1999 Wiley-Liss, Inc.     

Preferences of cardiologists and clinical geneticists for the future organization of genetic care in hypertrophic cardiomyopathy: a survey

In view of the increasing demands for genetic counselling and DNA diagnostics in cardiogenetics, the roles of cardiologists and clinical geneticists in the delivery of care need to be redefined. We investigated the preferences of both groups of professionals with regard to the future allocation of six cardiogenetic responsibilities in counselling and testing, using hypertrophic cardiomyopathy (HCM) as a prevalent model disease. In this cross-sectional survey, the participants were Dutch cardiologists (n = 643) and clinical geneticists (n = 60), all members of professional societies. Response rates were 33 and 82%, respectively. In both groups, the majority preferred to perform most of the tasks described above in collaboration. Informing HCM patients about the genetics of HCM and requesting DNA testing in symptomatic patients was viewed by 43 and 35% of cardiologists, respectively, as their sole responsibility, however, and 39 and 59% of clinical geneticists did not object to these views. Both groups felt that the task of discussing the consequences of HCM for offspring and that of discussing the results of DNA diagnostics should be shared or performed by clinical geneticists. Both groups considered co-ordination of family screening the sole responsibility of clinical geneticists. Opinions on who should request DNA diagnostics in asymptomatic relatives were divided: 86% of clinical geneticists considered it their exclusive responsibility, 10% of cardiologists believed that this task could be performed individually by either group and 30% preferred to collaborate. Most professionals said that they would appreciate education programmes and clinical guidelines. Both cardiologists and clinical geneticists prefer to share rather than divide most cardiogenetic responsibilities in caring for HCM patients. Consequently, capacity problems in both groups are to be expected. To safeguard current professional standards in genetic counselling and testing, deployment of non-medical personnel might be essential.     

Fetal mortality in sibships of cases with neural tube defects

It has been suggested that rates of fetal mortality in sibships of probands with a malformation inherited as a multifactorial threshold trait may reflect their liability to the malformation. If so, spontaneous abortion rates should be more frequent in sibships thought to have greater liability. For anencephaly and spina bifida (ASB), then, spontaneous abortion should be higher in the sibships of male probands and in families with more than one affected case (multiplex families). This hypothesis was tested using data on cases from The Montréal Children's Hospital and from the literature. Approximately 5000 pregnancies were analyzed. Rates of abortion did not vary with the sex or diagnosis of the proband. The spontaneous abortion rate was slightly higher in multiplex than in simplex families, but the difference was not statistically significant and most likely reflects the differing reproductive patterns in the two types of families. Thus, if male probands and multiplex sibships do have, on average, more liability for ASB, this liability cannot be detected in spontaneous abortion rates in the sibships available for this analysis.     

Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy

Female carriers of Duchenne muscular dystrophy (DMD) may demonstrate elevated serum creatine kinase (CK) and reduction of muscle dystrophin in all muscle types. We hypothesized that decreased dystrophin in uterine or pelvic girdle musculature might affect the obstetrical performance of females heterozygous for a dystrophin mutation. We reviewed the outcome of 34 deliveries resulting in 35 children from 13 women who were mothers of males attending a muscular dystrophy clinic. Obstetrical performance was examined retrospectively by chart review and patient contact. Of 35 children, 6 (17%) were delivered in the breech position, which is a fivefold increase above the national standards for term pregnancies. Of the six infants with breech presentation, two were males affected with DMD, one was a female heterozygote, one was a male who died perinatally, and the carrier status of the other two females is unknown. Most DMD affected males (12/14) were delivered in the vertex position. Thus, it is likely that maternal, rather than fetal, muscle weakness was the significant factor in determination of fetal position at term. We speculate that subtle changes in uterine or pelvic girdle muscle tone may contribute to a higher rate of fetal breech position in carriers of the DMD gene. Am. J. Med. Genet. 73:276–278, 1997. © 1997 Wiley-Liss, Inc.