American Journal of Medical Genetics 43:759-761 (1992)

Trisomy 18 and a Constitutional Maternal Translocation (2;18) Ikuko E. Teshima, Elizabeth J. T. Winsor, and Margot I. Van Allen Departments of Genetics and Pediatrics, The Hospital for Sick Children (I.E.T.,E.J.T.W., M.I.V.A.), Toronto; Department of Pathology, The Toronto Hospital (I.E.T.,E.J.T.W.), Toronto, and Department of Medical Genetics, University of British Columbia (M.I.V.A.),Vancouver, Canada Parental chromosomes are usually not analyzed in cases of trisomy 18 because the extra 18is assumedto have arisen through a meiotic nondisjunctionalevent. We report on a case of a trisomy 18 and a maternal translocation (2;18)(q34;q12). o 1992 Wiley-Liss, Inc. KEY WORDS: trisomy 18, parental translocation INTRODUCTION Autosomal trisomy of a whole chromosome resulting from the segregation of a reciprocal translocation involving the autosome has been reported in a few cases [Habedank and Faust, 1978; Hansteen et al., 1978; Fryns et al., 1986; Kotwaliwale et al., 19911. In these cases, the autosomal trisomy included the inherited balanced reciprocal translocation, and the extra chromosome was assumed to have resulted from a 3 :1segregation at meiosis I. In one report [Hansteen et al., 19781, the extra autosome was confirmed to be of maternal origin using a heteromorphic variant present in the maternal translocation carrier. In the case reported here, the trisomy 18does not include the parental translocation. We propose that this could have resulted from the formation of a chiasma between the centromere and the translocation breakpoint on 18q followed by a 3: 1 segregation at meiosis I. The only other case that we are aware of is a 47,XX,+13 prenatal result from a 46,XX,t(3;13)(q29;q22)translocation mother, reported in Daniel et al. [19891. CLINICAL HISTORY A female infant with clinical manifestations of trisomy 18 was born to a 28-year-old G1 woman following an uncomplicated pregnancy. There was spontaneous onset of labor at 35 weeks with severe variable decelera-

Received for publication July 31, 1991; revision received. Address reprint requests to Ikuko E. Teshima, Department of Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1x8, Canada.

0 1992 Wiley-Liss, Inc.

tions, and an emergency cesarean section was performed. Chromosome testing was ordered. The baby was severely depressed and died shortly after birth. The family refused an autopsy. The baby was small for gestational age (weight 1.36 kg) and had microcephaly (OFC 28.5 cm). The clinical phenotype was consistent with trisomy 18: prominent occiput, short palpebral fissures, fine facial features, highly arched palate, micrognathia, small posteriorly angulated ears, hypoplastic labia major,, and a short sternum. There was a loud systolic murmur with a gallop consistent with aventricular septa1defect. The abdomen was soft with possible horseshoe kidney. Parental chromosomes were examined following early spontaneous abortion of a second pregnancy. The products of conception were not available for chromosome analysis. The family history was said to be negative for spontaneous abortions, mental retardation, congenital abnormalities, or neonatal deaths. However, language difficulties limited full appreciation of the family history.

CYTOGENETICS Routine chromosomal analysis using GTG-banding of cultured lymphocyte chromosomes from the propositus showed a nonmosaic 47,XX, + 18 karyotype in 30 cells. The mother was found to have a reciprocal translocation with a 46,XX,t(2;18)(q34;q12)karyotype (Fig. 1).The father had a normal 46,XY karyotype. DISCUSSION Three possible explanations for the presence of the extra chromosome 18 in the infant are as follows: an interstitial chiasma and a maternal 3 : 1segregation at meiosis I with normal separation a t meiosis 11; a maternal nondisjunction at meiosis 11; a paternal nondisjunction at either meiosis I or 11. Brandriff et al. [1986] describe 23 different ways in which a reciprocal translocation may segregate to yield gametes. However, to explain the observation of the segregant type seen in the liveborn, two factors need to be considered. First, certain segregations may be preferred depending on the chromosomes involved and the breakpoint positions [Jalbert et al., 19801. Second, the via-

760

Teshima et al.

88

18 der 18

der 2 c

U

2

der2

C CJ

2

uu

Fig. 1. An ideogram and a G-banded partial karyotype of the maternal reciprocal translocation between 2q and 18q are shown at the left and upper right. The pachytene diagram at the lower right illustrates the proposed crossover in the proximal 18 long arms and the 3 :1segregation (indicated by the dotted lines) at meiosis I. The centromeres are designated as “c”.

bility of the segregant as a gamete or in the embryo may differ. In the case reported here, the formation of an interstitial chiasma is a reasonable possibility. In the few reports describing chiasma frequency and distribution in humans [Hulten, 1974;ISCN, 1985;Laurie and Hulten, 1985; Fang and Jagiello, 19881, chromosome 18 is thought to form one t o 2 chiasmata per bivalent. The chiasmata are localized at the long and short arm distal ends, and the preferred position is in the distal long arm; however, chiasmata are also found to occur in the proximal long arm. Although these studies are based on males, in females the preferred position for chiasmata between a pair of normal 18’s could also be in the long arm distal ends. If this is so, one could then postulate that in our female carrier, the distal long arm chiasma may have become displaced to a more proximal position because of the translocation (Fig. 1). Interstitial chiasmata are apparently not rare in translocation carriers [Chandleyet al., 1976;Palmer and Hulten, 1983;Laurie et al., 19841. A 3 :1 segregation at meiosis I is also a reasonable explanation for our case. One of the common findings in 3 :1 segregations, an asymmetrical quadrivalent [Lindenbaum and Bobrow, 1975;Jalbert et al., 19861, can be formed because the breakpoint in 2q is in the distal region, the breakpoint in 18q is in the proximal region

and chromosomes 2 and 18 are disparate in size. In addition, the 3: 1 segregant, trisomy 18 in this case, is compatible with live birth. An interstitial chiasma in the proximal long arm of 18, followed by a 3 :1segregation at meiosis I (Fig. 1)and a normal segregation at meiosis I1 will result in a gamete with one normal chromosome 2 and 2 normal 18’s, which with fertilization will result in trisomy 18. A gamete with the above chromosome complement could also arise through nondisjunction at meiosis 11; however, this mechanism is considered less likely. In sperm studies of translocation carriers, the 2 mechanisms, an interstitial chiasma with a 3 : 1segregation at meiosis I and a meiotic I1 nondisjunction, cannot be distinguished cytogenetically; DNA marker analyses are required. However, Brandiff et al. [19861 considered the former mechanism to be the most likely explanation for those specific sperm complements that could have arisen from either mechanism [Brandriff et al., 1986; Martin et al., 19901. That meiotic I errors occur more frequently than meiotic I1 errors has been documented for trisomy 21 [Dagna Bricarelli et al., 19891. These 2 mechanisms have also been used to explain the unusual segregation found in a translocation involving 11and 22 first reported by Lockwood et al. in 1989 [Lindenbaum, 19901. In our case, if maternal DNA marker analysis had been done, the centromericregions of 18would have

Wsomy 18 and Parental Translocation

been heterozygous if the mechanism had been an interstitial chiasmata and a 3 :1segregation at meiosis I and homozygous if the mechanism had been a meiotic I1 nondisjunction. A nondisjunctional event at either meiosis I or I1 in the father was also considered. The parental origin of the extra 18 was found to be maternal in 3 out of 3 informative cases in a study by Kondoh et al. [19881and in 19 out of 20 informative cases in a study by Kupke and Muller [19891. The predominance of maternal origin for the extra autosome has also been reported for trisomies 13 and 21 [Hassold et al., 1987; Dagna Bricarelli et al., 19891. Therefore, the explanation of a paternal error at either meiosis I or I1 is considered the least likely. Whichever the mode of segregation, this case illustrates that whenever a standard trisomy is found together with a clinical history of miscarriages, although the finding of a translocation will probably be rare [Uchida and Freeman, 19861, consideration should be given to the possibility of a translocation segregating in the family.

ACKNOWLEDGMENTS We thank the cytogenetics technologists at the Hospital for Sick Children and the Toronto Hospital for their work.

REFERENCES Brandriff B, Gordon L, Ashworth LK, Littman V, Watchmaker G, Carrano AV (1986):Cytogenetics of human sperm: meiotic segregation in two translocation carriers. Am J Hum Genet 38:197-208. Chandley AC, Seuanez H, Fletcher JM (1976): Meiotic behavior of five human reciprocal translocations. Cytogenet Cell Genet 17:98-111. Dagna Bricarelli F, Pierluigi M, Landucci M, Arslanian A, Coviello DA, Ferro MA, Strigini P (1989): Parental age and the origin of trisomy 21. A study of 302 families. Hum Genet 82:20-26. Daniel A, Hook EB, Wulf G (1989): Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements: Data from United States and Canadian laboratories. Am J Med Genet 33:14-53. Fang JS, Jagiello GM (1988):An analysis of the chromomere map and chiasmata characteristics of human diplotene spermatocytes. Cytogenet Cell Genet 4752-57. Fryns JP, Kleczkowska A, Moerman Ph, Van Den Berghe H (1986):

761

Reciprocal translocations and full trisomy (trisomy 18 and trisomy 21) in the offspring. Ann GBnBt 29:272-274. Habedank M, Faust J (1978): Trisomy 9p and unusual translocation mongolism in siblings due to different 3 : 1segregations of maternal translocation rcp(9;2l)(pll;qll). Hum Genet 42:251-256. Hansteen IL, Schirmer L, Hestetun S (1978): Trisomy 12p syndrome. Evaluation of a family with a t(12;21)(p12.l;pll)translocation with unbalanced offspring. Clin Genet 13:339-349. Hassold T, Jacobs PA, Leppert M, Sheldon M (1987): Cytogenetic and molecular studies of trisomy 13. J Med Genet 24:725-732. Hult6n M (1974): Chiasma distribution at diakinesis in the normal human male. Hereditas 76:55-78. Harden DG, Klinger HP (1985):“An International System of Human Cytogenetic Nomenclature (1985).” New York Karger. Jalbert P, Sele B, Jalbert H (1980):Reciprocal translocations: a way to predict the mode of imbalanced segregation by pachytene-diagram drawing. Hum Genet 55:209-222. Kupke KG, Muller U (1989): Parental origin of the extra chromosome in trisomy 18. Am. J . Hum. Genet. 45599-605. Kondoh T,Tonoki H, Matsumoto T, Tsukahara M, Niikawa N (1988): Origin of the extra chromosome in trisomy 18. A study of five patients using a restriction fragment length polymorphism. Hum Genet 79:377-378. Kotwaliwale SV, Dicholkar VV, Motashaw ND (1991):Maternal transmission of translocation 2;21 associated with Down’s syndrome. J. Med. Genet. 28:415-416. Laurie DA, HultBn MA (1985):Further studies on chiasma distribution and interference in the human male. Ann Hum Genet 49:203-214. Laurie DA, Palmer RW, Hultkn MA (1984): Studies on chiasma frequency and distribution in two fertile men carrying reciprocal translocations: One with a t(9;lO) karyotype and one with a t(Y,10) karyotype. Hum Genet 68:235-247. Lindenbaum RH (1990):Unusual segregation of constitutional llq;22q translocation may be explained by crossover in interchange s e g ment, followed by 3;l segregation at meiosis I. Hum Genet 85:143. Lindenbaum RH, Bobrow M (1975):Reciprocal translocations in man: 3 : l meiotic disjunction resulting in 47- or 45-chromosome offspring. J. Med. Genet. 12:29-43. Lockwood DH, Farrier A, Hecht F, Allanson J (1989):Not all chromosome imbalance resulting from the llq;22q translocation is due to 3 :1 segregation in first meiosis. Hum Genet 83:287-288. Martin RH, Barclay L, Hildebrand K, KOE, Fowlow SB (1990): Cytogenetic analysis of 400 sperm from three translocation heterozygotes. Hum Genet 86:33-39. Palmer RW, Hult6n MA (1983): Chiasma-derived genetic lengths and A reciprocal translocation recombination fractions: 46,XY,t(1;22)(q32;ql3). Hum Genet 47:299-310. Uchida IA, Freeman VCP (1986):Trisomy 21 Down syndrome. 11.Structural chromosome rearrangements in the parents. Hum Genet 72:118-122.

Trisomy 18 and a constitutional maternal translocation (2;18).

Parental chromosomes are usually not analyzed in cases of trisomy 18 because the extra 18 is assumed to have arisen through a meiotic nondisjunctional...
296KB Sizes 0 Downloads 0 Views