medical world medical genetics hungary* · medical genetics around the world journal of medical...

Medical genetics around the world

Journal of Medical Genetics 1988, 25, 2-8

Medical genetics in Hungary*A CZEIZELFrom the Department of Human Genetics and Teratology, WHO Collaborating Centre for the CommunityControl of Hereditary Diseases, National Institute of Hygiene, Budapest, Hungary.

The history of medical genetics in Hungary

The beginnings of medical genetics were promisingin the early decades of this century.1 The concept ofhereditary degenerative diseases was established bya Hungarian neurologist, Erno Jendrassik (1858-1921), in 1902. Another neurologist, Kairoly Schaffer(1864-1938), described the pathological basis ofTay-Sachs-Schaffer disease in 1905, and thus delin-eated the first inborn error of lipid metabolism.Karoly Csorsz (1892-1935) organised the first twinand population genetic studies, and the McKusickcatalogue2 gives him priority in describing X linkedrecessive ichthyosis (30810). Unfortunately in the1930s and early 1940s, the German influence and adrift towards fascism brought about the dominanceof an unscientific applied genetics which was used tomask vile political crimes. This programme divestedeugenics of its original character as envisaged byGalton. Naturally, many talented young medicaldoctors kept themselves aloof from medical geneticsand the active, decent medical geneticists wereovershadowed, for example, Kornel Korosy (1879-1948), who had previously written a monograph ongene linkage of great international reputation,3 orLip6t Szondi (1893-1986), who established a Gene-tic Registry of Handicapped Children in 1930. In the1950s Lysenko's doctrine also made scientific studiesin medical genetics impossible. The door wasopened again only in the early 1960s, owing to theactivities of molecular geneticists, but by that time ageneration of Hungarian geneticists was missing.Human cytogenetic methods were introduced byDezso Schuler, a paediatrician, in the early 1960s. Amilestone in the revival of Hungarian medicalgenetics was a 'refresher course of human genetics',

Received for publication 25 June 1987.Accepted for publication 7 July 1987.

*This review is in no sense 'official' as this evaluation of medical genetics dif-fers significantly from that of authorities of the medical health system and ofthe few full time geneticists in Hungary.

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organised by Gabor Szabo, a molecular geneticist,and supported by the WHO and the PostgraduateMedical School, Budapest, with the help of theDane Mogens Hauge and his coworkers in Tihany in1965. Another important event was the establish-ment of the first Hungarian genetic counsellingclinic in Budapest in 1963 by Georg Lenart (1896-1983), a paediatrician who was keenly interested inmedical genetics. In the meantime some of usgrasped opportunities to obtain short fellowships tolearn about recent developments in medical geneticsabroad. The first department of human genetics wasset up in the National Institute of Hygiene in 1971.An International Symposium on Medical Geneticssponsored by the WHO was held in Debrecen-Hajduszoboszl6 in 1976.4 The Hungarian Ministryof Health planned to found the National Institute ofHuman Genetics in 1978; however, owing to finan-cial problems it was postponed. The HungarianSociety of Human Genetics was created in 1972; atpresent it has about 260 members. The 18th Sympo-sium of the European Society of Human Geneticswas held in Budapest in 1985. The Department ofHuman Genetics and Teratology, National Instituteof Hygiene, was appointed as a WHO CollaboratingCentre for the Community Control of HereditaryDiseases in 1986.

A general view of the Hungarian population

Hungary has a population of 10-6 million people ofEuropean origin but more than three million Hun-garians live in the surrounding countries. There isonly one group in Hungary which differs from theHungarian stock: the gypsy population of about400 000 people. Genetic markers confirm that theyoriginate from north-west India. Their birth preva-lences of cleft palate, congenital cardiovascularmalformations, and congenital talipes enquinovarusexceed the usual Hungarian rate; however, theincidence of multiple sclerosis (MS) is lower. The

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increased rates are explained by the relatively highoccurrence of consanguinity; the frequency ofcousin marriages is between 2% and 20% indifferent gypsy samples, and is only 0.3% in thepopulation at large. The low incidence of MS isexplained by a peculiar HLA haplotype.

Hungarians are the descendants of a Finno-Ugrian population that settled in the Car-pathian basin in the last decades of the ninthcentury, after mass migration from different regionsof western Asia (around the Ural mountains) andeastern Europe. There was a close connection withTurkish, Iranian, and other populations during thelong migration and also with some Oriental-Mongo-loid and European populations that joined theoriginal group after the establishment of the Hunga-rian state. These historical events may explain theintermediate position of the Hungarian populationbetween the west European and east Orientalpopulations which is indicated by the distribution ofblood groups (ABO, Rh, etc) and by the 37%prevalence of lactose malabsorption. After thedisaster of Mohacs in 1526, a fatal defeat by theTurkish army, Hungary lost its political power inEurope and a considerable part of the populationwas destroyed during a Turkish occupation lastingnearly 150 years. Later it provided opportunities forthe different European groups to settle down in thisterritory. The lack of 'typical' Hungarian geneticdisorders is congruent with the high rate of hybridi-sation.The present demographic state of Hungary is

considered to be unfavourable. Recently the rate oflivebirths has dropped dramatically (figure). In 1956the Abortion Law let women decide whether or notthey wanted to have their pregnancies terminated.Subsequently the number of legally induced abor-tions increased continuously and peaked at 207 000in 1969. In contrast to the international trend, thislaw was restricted in 1974 for social reasons, butbroadened with respect to medical indications.Among the medical indications are those of agenetic-teratogenic nature. Abortion is permitted(1) before the 12th week when there is >10% riskof a severe, untreatable fetal disorder which is notdiagnosable prenatally; (2) before the 20th weekwhen there is >50% risk of a prenatally diagnosedfetal disorder; and (3) at any time when a lethaldisorder, incompatible with postnatal life, is diag-nosed prenatally. The occurrence of medicallyindicated induced abortions increased significantlyafter 1973 (figure). Fetal death, the third outcome ofpregnancy, occurs relatively infrequently; the ratesof recorded miscarriages and stillbirths were 13-1%and 0-8% respectively in 1975 to 1984. Infantmortality is decreasing, but even recent figures of

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coneleetc Id Indkiced ab,ortion0- without medical0 indication

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FIGURE Number of livebirths and induced abortions,together with the rate of recorded congenital anomalies (per100 total births) and genetic counsellees (per 100 liveborns).

about 2% considerably exceed the rates in de-veloped countries. The first day mortality is ex-tremely high because of the rigorous classification ofinfant deaths; this statement is in agreement withthe relatively low rate of stillbirths and the ex-tremely high frequency of newborns with a birthweight under 2500 g (about 10%). The mortalitypattern is also disadvantageous, as indicated by thelow life expectancy at birth: 65 6 years for males and73-7 years for females in 1984.

The present situation of medical and clinical genetics

There is an adequate number of physicians inHungary (with 34 548 in 1985, Hungary ranks fourthon the list of physicians/population rate in theworld), but there are only 25 human geneticists andonly five full time medical geneticists. However, ofthe above 25 human geneticists, 16 have sciencedegrees in addition. The requirements for 'humangenetics' as a medical specialty were regulated in1978. The minimal requirements of qualification forhuman geneticists are as follows: a four year practiceafter graduation and recommendation of the head ofthe institution; curriculum vitae and a list of publica-tions are also needed for this application. The boardof the Postgraduate Medical University, Budapest,decides on recognition without any examination (themajority of other medical specialties require exami-nation). Unfortunately, after the first year (1979),the number of physicians with the qualification ofhuman geneticist has been very low. A postgraduatecourse of medical genetics has not been organised inthe past 10 years. (An exception was a prenatal

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diagnostic course in Debrecen in 1984.) Otherpostgraduate medical courses, mainly in paediatricsand gynaecology-obstetrics, have some genetictopics within their 60 hour courses. Thus, presentpostgraduate education is inadequate for providingtraining and for stimulating and supplying thenecessary replacements, that is, a new generation ofmedical geneticists. Additionally, four medical uni-versities have no independent institutions for humanor medical genetics. The principles of moleculargenetics are taught within the subject 'biology' in thefirst year of the six year medical curriculum. A'clinical genetics' course of two to 24 hours is taughtby the staff of biological, paediatric, or obstetricinstitutes in the fifth year. However, at the end ofthis course an examination is required only at twouniversities, whereas at the other two universities itis included in paediatrics. In general, this amount ofeducation is not enough to arouse the interest ofmedical students in medical genetics. It explains theinadequate knowledge of medical genetics ofmedical graduates and the difficulty of attractingyoung medical doctors for genetic counselling out-patient clinics.

Clinical genetics is pursued in paediatric inpatientclinics in four medical universities (Budapest,Debrecen, Pecs, and Szeged) and some countyhospitals (Gyor, Szombathely) by qualified medicalgeneticists. Four prenatal diagnostic centres (Buda-pest: Postgraduate Medical School, Debrecen, Pecs,and Szeged) function within obstetric inpatientclinics. Both chorionic villus sampling and transab-dominal amniocentesis are used after ultrasoundscanning for this purpose. (These procedures areperformed on pregnant women admitted to hos-pital.) The group of clinical geneticists headed by ZPapp in Debrecen has achieved a high standard ofprenatal diagnosis and postgraduate teaching. Thenational policy on indications for prenatal diagnosishas been determined by official guidelines. Thegeneral principle is that prenatal diagnosis is reason-able in cases in which there is >2% risk of severefetal disorders that cannot be effectively treated. Ingeneral, this procedure is offered by genetic counsel-ling clinics; however, the heads of Prenatal Diag-nostic Centres consider the maternal indications foramniocentesis or chorion biopsy. Until 1984, therewas a fifth Prenatal Diagnostic Centre with a highstandard of cytogenetic methods; however, after thehead retired it was not possible to find an adequatesuccessor. The use of biochemical methods is limitedand DNA probes have not been introduced intoHungary, though some groups are making efforts touse them in clinical practice*. There are only two

*Note added in proof. This method is available now in cystic fibrosis,Duchenne muscular dystrophy, and haemophilia A.

well established biochemical laboratories mainlyinterested in medical genetics (paediatric clinics inPecs and Szeged).

Technical facilities, including equipment, re-agents, kits, etc, have lagged behind rapid inter-national developments. At present this gap causesserious difficulties for both medical services andresearch. Consequently, our strategy is to concen-trate our research efforts only on certain topics withexpertise and a good tradition, for example, studieson haemoglobinopathies,5 6 minor anomalies,7 andpharmacogenetics,8 or with special advantages froman international viewpoint, for example, populationbased studies that are easier to undertake inHungary than in some developed countries.The social appreciation of medical genetics is

controversial in Hungary. The consequences ofprevious political events (fascist eugenics and thestatement that genetics was a 'guilty' and reaction-ary science in the 1950s) cast a shadow of suspicionon medical genetics. The lack of appreciation orunderstanding of the discipline may also stem fromthe fact that there are no independent institutions ofmedical genetics in Hungary. In addition, thecurrent leaders of the health system lack anyeducation in medical genetics and this fact mayexplain why they consider genetic disorders to berare and generally untreatable. Genetic susceptibili-ties to common diseases are not recognised andconsequently not used in preventive programmes.Furthermore, the importance of some originalapproaches may not be understood, as indicated bythe following example. In 1977, the PhD applicationof Zoltan Kazy (in Hungary this corresponds to thedegree of candidate of sciences) was accepted sothat he was able to undertake prenatal geneticresearch in Moscow. Under the direction of I SRozovsky, he pursued studies on early pregnancyand soon established a routine method of chorionbiopsy at six to 12 weeks of gestation following theultrasonic or transcervical embryoscopic localisationof chorion frondosum. The genetic study of sexchromatin and enzymes in these fetal tissues provedto be successful in pregnant women in 1978. Theseresults were published in Hungarian in 1979 and inEnglish in 1982.9 After his return to Hungary, hereceived no help to continue this pioneer work andthus lost his favourable position.

Organisation and concept of genetic counselling

After some spontaneously established genetic coun-selling outpatient clinics, a national network was setup in 1976 as part of the National Mother and ChildCare System. This network is directed by theNational Institute of Gynecology and Obstetrics.

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The choice of this base was a poor decision whichhas caused a decrease in the standard of geneticcounselling.On the one hand this Institute cannot provide

adequate guidelines for genetic counselling becauseit has no experience in this field. On the other handthe financial support comes through the budget ofthe Family and Female Counselling Clinics and theshare of Genetic Counselling Clinics is decided bygynaecologists; thus, these institutions 'are under-supported. Additionally, no consideration is givento case load when funds are allocated: geneticcounselling clinics with 3000 or 100 new counselleesper year are given the same amount. At presentthere are 13 genetic counselling outpatient clinics in

Hungary, six in Budapest with 2 million inhabitantsand seven in the remainder of the country with 8-6million persons. The head of each genetic counsel-ling clinic is a medical doctor (seven paediatricians,three gynaecologists, three medical geneticists) andnearly all genetic counselling clinics have a suitablecytogenetic laboratory and clinical backup as well as

auxiliary personnel. (Of 16 medical cytogeneticlaboratories in Hungary, 11 work directly with or

closely connected with genetic counselling clinics,three others are involved with tumour cytogenetics,one is located in a paediatric clinic in Debrecen, andanother in a forensic institute in Budapest.) Thegenetic counselling clinics cover a defined territory.All clinics are prepared to deal with all types ofgenetic disorders but some also specialise in certaintypes of genetic diseases. As a result of exposure inthe Hungarian media, medical genetics has gainedhigh popularity in the population and explains thehigh participation rate in genetic counselling clinics.The number of new counsellees continues to in-crease; at present four consultations per 100 live-born infants are recorded yearly (figure). In addi-tion to formal genetic counselling, advice con-

cerning teratogens is also given by these clinics andthis special group represents about 15% of counsel-lees. Since 1987 there has been an attempt to lowerthis proportion by providing a centralised telephonecounselling service.

In the early 1970s, the traditional non-directivemethod of counselling was introduced. However,Hungarian counsellees were not satisfied with thisbecause they expect more help from counsellorsthan mere information. More exactly, they asked forspecific advice-guidelines to make an appropriatechoice among several options. To satisfy the re-

quirements of the counsellees so-called 'informa-tion-guidance' counselling was established.'0 (Thisterm was coined with the help of the late Professor CO Carter.) First, the nosological diagnosis must beclarified. In our clinic 60% of probands are referred

with a diagnosis, in another 20% this diagnosis isestablished as a result of supplementary examina-tions during the counselling investigations, while inthe final 20% a diagnosis cannot be established.Secondly, the explanation of the so-called 'danger'or 'burden' involves (1) the severity of the expecteddisorder, (2) the possibilities of treatment, (3) thesuitability of prenatal diagnosis, (4) the magnitudeof the genetic risk, (5) the maternal risk duringpregnancy, (6) the teratogenic risk of maternaldisease and its treatment during pregnancy, (7) thepostnatal risks connected with affected parents, forexample, a schizophrenic or alcoholic mother, (8)the coping potential of the family, (9) the socio-economic situation of the family, and (10) thenumber of previous affected or unaffected children.Thirdly, if counsellees want our advice, we sum-marise it after we obtain informed consent fromthem to be guided about their choices in reproduc-tion. Each genetic counselling session is individual;however, the counselling situations can be groupedinto five general categories of advice (table 1). Afterthe 'persuasive' advice of categories I, II, and III,95% of counsellees want to have a baby. After the'dissuasive' advice of categories IV and V, 61% ofcounsellees are deterred. Of course, we do our bestto help the remaining 39% with no compliance. Wehope that this Hungarian counselling method suitsthe original Galtonian idea (that the task of medicalgeneticists is to inform and counsel, while thedecision is the right and responsibility of counsel-lees), the expectation of our clients based on theircultural tradition, and human rights in general.Nevertheless, the ethical issues of our practical workhave been highlighted and are continuously discus-sed within society."There are some serious difficulties in the practical

work of genetic counselling, the majority of which

TABLE 1 Distribution of consultands according to fivecategories of 'advice'.

Category Meaning Percent Undeterred Proportion (%)of advice (%) of affected sibs

(bv specificand non-specificanomalies)

I No essential problem.pregnancy recommended 20 96 3

II Pregnancy recommendedafter some preparation 65 94 6

III Pregnancy recommendedwith prenatal fetalexamination 5 90 2

IV There is some problem.pregnancy requiresconsideration 5 40 20

v There is a serious problem,pregnancy is notrecommended 5 38 44

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are connected with the lack of adequate coordina-tion of the work of counselling. The lack of cleardirection explains why the criteria for qualifyingthose who do genetic counselling are not prescribed.Recently, medical doctors and biologists withoutany qualifications have been doing genetic counsel-ling. Finally, the lack of necessary consensus inmethods used in counselling has caused a decreasein counselling standards. This became obvious afterassessing the extreme variation in counselling givenafter the Chernobyl accident and after evaluatingthe international variation in an international crosscultural study of ethics and human genetics.12 Thelack of independent representation of medical gene-tics may explain some of the ethical mistakes inofficial regulations, for example, a directive methodof premarital counselling, the exclusion of womenover 40 from heterologous artificial insemination,and the legal prohibition of sterilisation in males (infemales it is allowed under certain conditions)*. Thepoint is that Hungarian medical geneticists have tofight for some independence in their own field.

Optimal family planning programme

Parallel with the increasing popularity of geneticcounselling, a growing number of couples withoutsignificant specific risk factors seek advice in geneticcounselling clinics with the desire of having 'perfect'(in Hungary 'optimal') babies. On the one hand theywant to do their best and to use modern methods offamily planning in order to decrease the randomrisk. On the other hand they have not been satisfiedwith the obligatory premarital counselling, whichseemed to be a bureaucratic procedure without anymedical benefit. This frequent wish has prompted usto combine some available methods in an 'OptimalFamily Planning Programme' supported by theWHO to prevent some specific disorders and toreduce random risk. This programme has threeguiding principles.

I Checking reproductive health. This is based onseven points: (1) family history of both partners (todetermine whether or not it is worthwhile visitingthe genetic counselling clinic), (2) case history of thefemale to reduce any maternal risk, for example,diabetes mellitus or epilepsy, that may exist, (3)pregnancy fitness (special gynaecological examina-tion for the detection of anomalies or inflammationof the reproductive organs and hormonal distur-bances), (4) male procreativity fitness (sperm analy-sis), (5) exploration of psychosexual life (whether ornot it is worth visiting a sexologist), (6) occupationalhistory, and (7) exclusion of some specific risks, for

*This regulation was changed on 1 September 1987.

example, rubella seronegative females are vac-cinated, toxoplasma seronegative females are fol-lowed up serologically, and anaemia is treated bymultivitamins.

II A three month preparation for conception.Conception is prepared for by (8) protection of germcells (advice to stop smoking, drinking alcohol,unnecessary medication, etc), (9) restoration ofhormonal balance after using the contraceptive pill(the rate of use is 45%), (10) estimating two optimaldays for conception by basal body temperature, (11)administration of a preconceptional multivitamin(Elevit PronatalR-Roche) supplement.

III Protection of very early pregnancy. At the endof the three month preparation period couples ingeneral (92%) get a 'start' signal to commenceconception and females are asked to visit expertsimmediately after the first missed menstrual period.This principle aims (12) to achieve pregnancy in theoptimal days of conception, (13) to diagnose preg-nancy at a very early stage by a sensitive pregnancytest (in general it is also confirmed by ultrasoundscanning), (14) to exempt the fetus from hazards,for example, any previously detected occupationalhazards, (15) to continue postconceptional multi-vitamin supplementation up to the 10th week ofgestation. After the 10th week of gestation pregnantwomen are referred to antenatal care clinics. In thefirst 1000 outcomes of pregnancy, the best result wasa more than 50% decrease in livebirths of low birthweight.

Public health programmes

Congenital anomalies (CA) have an increasingpublic health importance. In Hungary they comprise6% of all births. CA as a group is the eighth leadingcause of death and the second largest cause of infantmortality accounting for 23% in Hungary in the1980s. Altogether they cause nearly 5000 years oflost life and about 4500 years of actually impairedlife within our population each year.The Hungarian Congenital Malformation Regis-

try was established in 1962 based on obligatorynotification of CA diagnosed in malformed indexpatients from birth up to the age of one year.Notification is exclusively the task of physicians:obstetricians (all deliveries take place in hospital),paediatricians (inpatient and outpatient clinics), andpathologists (necropsy is obligatory). Data arecritically evaluated before registration, for example,isolated and multiple CA are separated rigorouslybecause, in general, isolated CA entities could beconsidered to be nosological ones while componentCA within multiple CA are of heterogeneous origin.Recently recorded total figures of CA have been

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near to 5% of total births (figure). Validity ofdiagnoses and completeness of ascertainment arechecked in ad hoc epidemiological studies; thus truebirth prevalences of common CA (birth prevalence.1 per 1000 births13) and moderately frequent CA(0-1 to 0-99 per 1000 births) are known (table 2).Since 1973 other surveillance programmes havebeen based on this Registry within the Centre ofCongenital Anomaly Control. Here only two will bementioned.The national follow up programme of multimal-

formed babies'4 has three purposes. (1) To increasethe rate of identified multiple CA entities (thesuccess rate increased from 33% to 50%). (2) Toattempt the delineation of further recognisable CApatterns since their identification helps to estimatethe prognosis and sib occurrence. (3) To establish aspecial surveillance for the detection of environ-mental mutagens because mutant genes, owing totheir pleiotropic effect, and microscopically visiblechromosomal aberrations, owing to their general-ised impact, in general cause multiple CA.The purpose of the Surveillance of Indicator

Conditions is to estimate the occurrence of newgerminal mutations. The so-called indicator condi-tions in offspring are or may be distant phenotypicmanifestations of altered DNA in germ cells of theparent. This surveillance involves three indicatorconditions checked by personal or cytogenetic ex-amination and completed by the family history: (1)15 sentinel anomalies as indicators of germinaldominant gene mutations; 46 new mutations peryear were detected in 1980 to 1984; (2) Down'ssyndrome as an indicator of germinal numericalchromosomal mutations; its birth prevalance is 1-2per 1000 total births and 98% occurred as a de novoevent; (3) pairwise analysis of component CA withinunidentified multiple CA. Ten year baseline figures

TABLE 2 True birth prevalence and sib occurrences of 10common congenital anomalies in Hungary.

Congenital anomaly True birth Sib occurrenceprevalence (%)per 1000total births

*Congenital liability for dislocation 28-00±0-98 14of hip (Ortolani click)

Congenital inguinal hernia (operated) 11 04±1-29 10Undescended testes 6-7±0 62 7

(in brothers)Neural tube defects 2-80±0-40 3Hypospadias 2-2±0-32 5

(in brothers)Congenital hypertrophic pyloric stenosis 1-46±0-20 6Ventricular septal defect 1-39±0-47 3Structural talipes equinovarus 1 30±0-38 6Down's syndrome 1-2±0-18 1Cleft lip ± palate 1-03±0-20 5

*See text.

of these sets were determined in 1973 to 1982 andrecent annual figures are compared with them.

Multiple births in women in Budapest and itssurrounding area have been recorded by the Buda-pest Twin Registry since 1 January 1970. Everyobstetric institution is obliged to notify every mul-tiple delivery and the completeness of notificationsexceeds 90%. Placentas are collected and examinedby the same pathologist. In like sexed twins with adichorionic placenta, zygosity is determined be-tween the ages of three and six years by examinationof blood and serum protein groups. The zygosity oftwins born between 1970 and 1979 was determinedin 78-7% of all pairs. Congenital structural talipesequinovarus, congenital inguinal hernia, hypo-spadias, and undescended testes are significantlymore frequent while the occurrence of congenitalhypertrophic pyloric stenosis is significantly lower intwins.

There are four preventative programmes con-cerned with genetically determined disorders. (1)Maternal serum AFP (MS-AFP) screening is under-taken in the 16th week of gestation with ultrasoundexamination and, if necessary (after repeated posi-tive MS-AFP values with negative ultrasound scan-ning), amniotic AFP examination. This programmebecame population based in 1985, but the efficacy islow. In 1984 to 1985 331 cases with isolated neuraltube defects were recorded but the necessary datawere only available in 279 for further analysis. Only79 were prenatally diagnosed before the 22nd weekof pregnancy and only 74 of the pregnancies wereterminated. However, of the remaining 200 births,188 were examined by MS-AFP and 161 by ultra-sound. MS-AFP indicated a positive finding in 94cases (50%) while ultrasound demonstrated a neuraltube defect in 22 cases. The lack of elective abortionwas explained by deviation in results of two exami-nations, mothers did not want to terminate theirpregnancies, or examinations were performed toolate. (2) Prenatal chromosome examination isundertaken in fetuses of mothers over 40 years ofage. Only 23-4% of pregnant women in this categorywere examined in 1984 to 1985 and 16 numericalchromosome aberrations were detected (2-6% of allfetal chromosome analyses). This is far from thedesired goal. (3) Newborn screening for phenyl-ketonuria (PKU) became a population based pro-gramme in 1973. Later, galactosaemia and hypo-thyroidism were added to the screening. This pro-gramme seems to work well; the recorded birthprevalence of PKU is 0-09 per 1000. (4) Orthopaedicscreening of newborns is undertaken which hasresulted in almost total prevention of Hungary'smost common CA, dislocation of the hip. Theproblem is that the screening has resulted in

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overdiagnosis which has greatly increased the birthprevalence of this CA (28 per 1000 compared withthe prevalence of manifest cases of about 10 per

1000 in the 1940s). At present there is an effort tomake the diagnosis more reliable.

Conclusion

Two features, among others, are characteristic formedical geneticists and allied specialists in Hungary.On the one hand there is dissatisfaction withavailable conditions of practice in the light of theincreasing opportunities provided by new develop-ments in medical genetics. On the other hand thereis optimism due to the belief that the time has cometo be able to prevent severe genetic disordersshowing as a precedent how an apparently fixeddestiny may be overcome.

I am grateful to Professors J Miller (Osaka), LAlfody (Szeged), and G Szabo (Debrecen) for helpin improving the text.

References

Czeizel A. A historical evaluation of the doctrine of heredode-generation. Communications De Historia Artis MedicinaeBudapest 1979;87-88:157-79.

2 McKusick VA. Mendelian inheritance in man. Catalogs ofautosomal dominant, autosomal recessive, and X-linked pheno-types. 5th ed. Baltimore: Johns Hopkins University Press, 1978.

3Krosy VK. Versuch einer Theorie der Genkoppleung. Biblio-theca Genetica XV. Leipzig: Verl V Gebruder Borntraeger,1929.Szab6 G, Papp Z, eds. Medical genetics. Amsterdam, Oxford:Excerpta Medica, Budapest: Akademiai Kiad6, 1977.

5Hollan SR, Szelenyi JG, Lehmann H, Beale D. A Boston-typehaemoglobin M in Hungary: haemoglobin M Kiskunhalas.Haematologia 1967;1:11-7.

6 Hollan SR, Szelenyi JG, Brimhall B, et al. Multiple alpha-chainloci for human haemoglobin: Hb J Buda and Hb G Pest. Nature1972;235:47-50.Mehes K. Minor malformations in the neonate. Budapest:Akademiai Kiad6, 1983.Sz6r5dy I. Pharmacogenetics: principles and pediatric aspects.Budapest: Akademiai Kiad6, 1973.Kazy Z, Rozovsky IS, Bakharev VA. Chorion biopsy in earlypregnancy: a method of early prenatal diagnosis for inheriteddisorders, Prenat Diagn 1982;2:39-45.

'0 Czeizel A, Metneki J, Osztovics M. Evaluation of information-guidance genetic counselling. J Med Genet 1981;18:91-8.Czeizel A. The right to be born healthy. (Ethical problems ofmedical genetics.) Budapest: Akademiai Kiad6-Alan R Liss,1987.

12 Fletcher JC, Wertz DC. Ethics and human genetics: a cross-cultural perspective. Heidelberg: Springer (in press).

'3 Czeizel A, Tusnady G. Aetiological studies of isolated commoncongenital abnormalities in Hungary. Budapest: AkademiaiKiad6, 1984.

4 Czeizel A, Telegdi L, Tusnady G. Multiple congenital abnor-malities. Budapest: Akademiai Kiad6 (in press).

Correspondence and requests for reprints to Dr ACzeizel, National Institute of Hygiene, Gyaili ut 2-6,H-1097 Budapest, Hungary.

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