In view of the increased frequency of chromosome rearrangements demonstrated in these couples and the importance of counseling for future pregnancies, it would be wise to consider cytogenetic evaluation when all other probable causes for recurrent abortion have been ruled out

Chen, Andrew T. L.

English, Susan

Heritage, Deborah W.

Young, Reuben B.

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Chromosome Abnormalities and Repeated Abortion: A Preliminary Report SUSAN ENGLISH, B.A., DEBORAH W. HERITAGE, B.A., M.S., ANDREW T. L. CHEN, PH.D., REUBEN B. YOUNG, M.D. Program In Human Genetics and the Department of Pediatrics, Medical College of Virginia, Health Sciences Division, Virginia Commonwealth University, Richmond The role of chromosome aberrations in the etiology of early spontaneous abortions has been well established (1). Various investigators have found that 25-35% of all such abortions are the result of cytogenetic abnormalities (2, 3). The great majority of these aberrations are believed to be the result of de nova errors in meiosis and only rarely can early mitotic mistakes account for these events (3). In a minority of cases, one of the parents may harbor a transmissible chromosome anomaly. The carrier is apparently physically normal and has a balanced genetic make-up compatible with life. Dur-ing gametogenesis, however, unequal gametes may be formed, resulting in development of a nonviable zygote. This may predispose the carrier to recurrent early abortion of his or her offspring. Recently, a number of studies have attempted to find such a correlation between recurrent pregnancy loss and parental chromosome anomalies (3, 4, 5, 6). An investigation of this type was initiated at the Medical College of Virginia in the fall of 1973. Letters were sent to obstetricians in eastern Virginia requesting referrals of patients with histories of two or more spontaneous abortions. Blood was drawn from both the husband and wife and karyotype anal-ysis was performed according to conventional meth-ods. Five anomalies have been ascertained in the 25 couples studied so far. A discussion of the sig-nificance of these findings is considered below. A 28-year-old white female was found to have a modal chromosome number of 47. The patient was MCV QUARTERLY 10(3): 163, 167, 1974 intelligent and physically normal with a history of two spontaneous abortions and no live births. Karyo-type analysis, banding studies, and buccal smears showing two sex chromatin bodies in 31 % of 800 cells analyzed confirmed that the patient was a triplo-X female. The incidence of 47,XXX females is believed to be about one per 1000 in the normal population (7) . Due to wide phenotypic variability, a clearly defined triplo-X syndrome has not been established. Fertility is thought to be unimpaired (8). There is, however, a slightly increased risk of sex chromosome anomalies in the offspring. Chromosome polymorphism was detected in a 30-year-old white female with a history of two early spontaneous abortions. Satellites on chromosome 17 were seen consistently in all preparations. A poly-morphism of this type is not believed to contribute to repeated fetal wastage ( 4), although the possi-bility cannot be ruled out until prospective studies are done. The patient was in the seventh month of an uneventful pregnancy when the study was done. Another structural polymorphism was discov-ered in a husband whose wife had experienced three spontaneous abortions and no live births. The hus-band's karyotype was 46,XY with an enlarged # 16 chromosome. The clinical significance of this finding is not known at present, and the patient's chromo-somes are being studied with banding techniques. One of the most interesting findings was the as-certainment of two families with balanced D/ D (Continued on page 167) 163 ENGLISH ET AL: CHROMOSOME ABNORMALITIES AND REPEATED ABORTION 167 (Continued from page 163) translocations. In the first family, the husband was the carrier and exhibited a 45,XY t(DqDq) cell line. His wife had experienced three spontaneous abor-tions, had given birth to a normal female, and a hy-drocephalic female who died in infancy. In a pedigree study, the patient's mother, brother, sister, and sis-ter's son were all ascertained as carriers (Figure 1). In the second family, the wife was found to have the same type of D/D translocation. The patient had two normal sons and three early spontaneous abor-tions. One of the patient's sons is a carrier. Pedigree studies are incomplete in this family as of this writing. Translocations in patients selected for investiga-tions of this nature may be as frequent as one in 53 (6). Thus, about 1 in 26 couples with a history of habitual abortion may be found to exhibit a translocation. The frequency of t(DqDq) in the nor-mal population is believed to be one per 1000 ( 9). As in our study, this specific rearrangement is the single most frequent finding reported in cytogenetic evaluation of couples experiencing recurrent abor-tion (3). Since both t(DqDq) patients in our study have produced normal offspring, both must harbor heter-ologous translocations. Analysis is continuing in both families to detect which D group chromosomes are involved and to locate other carriers in relative~. The major question in this investigation is whether observed chromosome anomalies are caus-ally related to repeated fetal wastage. Based on previous reports, there does not seem to be an in-creased risk of abortion in a triplo-X female or pa-tients with · satellites on chromosome 17 ( 4, 7, 8). Due to the increase in sex anomalies in offspring of triplo-X females, however, amniocentesis at 14-16 weeks of pregnancy is indicated in these cases. Wide phenotypic variability in both male and female off-spring with an extra X chromosome makes counsel-ca rri e r o~· ~-spon t an e ous aborti on JZ[ deceased * no t s t udied FIG. I-Pedigree of a family showing inheritance of a D / D Robertsonian translocation. ing difficult, but families need to be advised of the potential risks involved. In this particular patient with a triplo-X karyotype, the extra chromatin ma-terial appears to be innocuous in terms of her own physical manifestations. In the case of the large # 16, chromosome banding techniques should shed light on the structural polymorphism involved. In all three cases, only prospective studies will give more precise counseling information. In the two couples with D / D translocations, we believe the rearrangements are related to recur-rent spontaneous abortion. Amniocentesis is indi-cated in any future pregnancy due to the increased risk of an offspring with D-trisomy. A study is currently in progress to examine, with recently developed banding procedures, karyo-types of all patients seen to date. In this way anom-alies unrecognized with the standard procedure may be detected. These hidden aberrations may be re-sponsible for repeated fetal wastage in certain cases. In view of the increased frequency of chromo-some rearrangements demonstrated in these couples and the importance of counseling for future preg-nancies, it would be wise to consider cytogenetic evaluation when all other probable causes for recur-rent abortion have been ruled out. REFERENCES I. CARR DH : Chromosomes and abortion. Adv Hum G enet 70:201, 1971. 2. LARSON S, TITUS J: Chromosomes and abortions. Mayo Clin Proc 45: 60, 1970. 3. BHASIN M , FOERSTER W, FUHRMANN W: A cytogenetic study of recurrent abortion. Humangen etik 18 : 139, 1973. 4. DE LA CHAPELLE A, SCHRODER J, KOKKONEN J: Cyto-genetics of recurrent abortion of unsuccessful preg-nancy. Int'! I Fertil 18:215, 1973. 5. KAOSAAR M , MIKELSAAR A : Chromosome investigation in married couples with repeated spontaneous abortions. Huma11ge11etik 17:277, 1973. 6. LUCAS M, WALLACE I, HIRSCHHORN K : Recurrent abortions and chromosome abnormalities. I Obstet Gynaec Br Comm 79: 1119, 1972. 7. LUCAS M, DEWHURST C, HURLEY R , ANDERSON S, BLUNT S : A search for triple X females in a fertile population . I Obstet Gy11aec Br Comm 78 : 1087, 1971. 8. BARR M , SERGOVICH F, SHAVER E: The triplo-X female: An appraisal based on a study of twelve cases and a review of the literature. Ca11ad M ed Assoc J IOI :247, 1969. 9. HAMERTON J: Huma11 Cytogenetics. New York/ London , Academic Press, 1971. 

Chromosome Abnormalities and Repeated Abortion: A Preliminary Report

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Chromosome Abnormalities and Repeated Abortion: A Preliminary Report

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