Prenat. Diagn. 19: 282–286 (1999)

SHORT COMMUNICATION

Prenatal Diagnosis of a Satellited Non-acrocentric ChromosomeDerived from a Maternal Translocation (10;13)(p13;p12) andReview of Literature

L. Faivre1, N. Morichon-Delvallez1, G. Viot1, A. Larget-Piet2, F. Narcy3, C. Turleau1, M. P. Pinson1,Y. Dumez4, A. Munnich1 and M. Vekemans1*1Departement de Genetique, Hopital Necker Enfants Malades, Paris, France2Service de Cytogenetique, Centre Hospitalier, Angers, France3Service d’Anatomopathologie, Hopital Port-Royal, Paris, France4Centre de Medecine Foetale, Hopital Necker Enfants Malades, Paris, France

We identified a familial balanced translocation involving chromosomes 10 and 13 through the finding of asatellited 10p chromosome in a fetus. The phenotype of two unbalanced products of the translocationresulting in pure monosomy 10p13 and trisomy 10p13 is described. This familial case and two of ourunreported cases are discussed in the light of other prenatal observations with satellited non-acrocentricchromosomes reported in the literature. Copyright ? 1999 John Wiley & Sons, Ltd.

: satellited non-acrocentric chromosome; prenatal diagnosis; genetic counselling

INTRODUCTION

Satellited non-acrocentric human chromosomes resultfrom translocation of genetic material from the shortarm of an acrocentric chromosome on anotherchromosome. Several instances describing such trans-locations are available in the literature and were par-tially reviewed by Estabrooks et al. (1992). They areusually diagnosed postnatally and are ascertainedthrough an abnormal phenotype resulting from thesegregation of a balanced parental translocation. Here,we describe the existence within the same family of apure monosomy 10p13 and a pure trisomy 10p13diagnosed prenatally and resulting from the segre-gation of a maternal balanced translocation involvingchromosomes 10p and 13p. In addition, a review of theliterature of similar observations provides some guide-lines for the genetic counselling of such cases.

CASE REPORT

An amniocentesis was performed at 23 weeks of ges-tation in a 33-year-old woman (III-2) because of thediscovery at ultrasound of intra-uterine growth retar-dation (3rd percentile), left ventricular dilatation, shortlimbs (10th percentile), nuchal web and retrognathismin the fetus. Maternal familial history revealed that shehad lost her first pregnancy, and had had a healthy girl(Fig. 1). Her first and second cousins were mentallyretarded (III-3, IV-5). Paternal familial history wasuneventful. Pregnancy termination was performed at

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26 weeks of gestation after genetic counselling and thediscovery of a deletion of chromosome 10p resultingfrom the segregation of a maternal balanced trans-location involving the short arms of chromosomes 10and 13. The autopsy revealed a female fetus with facialdysmorphism including hypertelorism (Fig. 2(B)). Inaddition, a cerebral ventricular dilatation and anunicornis uterus were observed. X-rays of the fetusshowed a delayed bone maturation.

The fourth pregnancy of this couple (IV-4) wasmonitored by amniotic fluid karyotyping at 13 weeksof gestation. This pregnancy was also terminated at 16weeks of gestation after genetic counselling because ofthe discovery of a trisomy 10p resulting from thesegregation of the maternal translocation. An autopsywas performed and showed a male fetus, small forgestational age (between 3rd and 25th percentile), withthin limbs, camptodactyly of the fingers and facialdysmorphism including brachycephaly, retrognathism,small mouth with thin lips, low-set and posteriorlyrotated ears with lobes attached (Fig. 2(A)). X-rays ofthe fetus were normal for the term.

*Correspondence to: M. Vekemans, Service de Cytogenetique, Hopi-tal Necker Enfants Malades, 149 Rue de Sevres, 75015 Paris, France.

CYTOGENETIC ANALYSIS

Chromosome analysis of the parents was performed onblood samples while cytogenetic analysis of the fetuseswas performed on amniotic fluid cells. Solid Giemsa,NOR, RHG, GTG banding, and fluorescence in situhybridization (FISH) were used. Chromosome analy-sis of the father was normal. The mother presenteda balanced translocation involving the short armsof chromosomes 10 and 13. Her karyotype was

Received 13 July 1998Revised 6 October 1998

Accepted 10 October 1998

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46,XX,t(10;13)(p13;p12) (Fig. 3(B)). The first fetus hadinherited an unbalanced translocation resulting in adeletion 10p13 with karyotype 46,XX,der(10)t(10;13)(p13;p12)mat (Fig. 3(A)). The second fetus had inher-ited another unbalanced product of this translocationresulting in a trisomy 10p13 with karyotype 46,XY,der(13)t(10;13)(p13;p12)mat.

Cytogenetic analysis of the family showed that thetranslocation was inherited from the maternal grand-father (II-4). Unfortunately, no cytogenetic study wasavailable on the first pregnancy. No blood sample wasavailable for II-3 and III-5 but we can presume that themental delay resulted from the presence of an unbal-anced product of the familial balanced translocation.

Fluorescence in situ hybridization (FISH) analysiswith a chromosome 10 specific subtelomeric probe(CTBQ 14 15, locus 10p15) was performed on the

Copyright ? 1999 John Wiley & Sons, Ltd.

mother and the fetuses (Fig. 4). These studies con-firmed the results of the cytogenetic analyses.

Fig. 1—Family pedigree. Affected fetuses are shown in black, and carriers of the balanced translocation are shown in blackand white. Individuals with mental retardation and unknown cytogenetic status are hatched. (?) Chromosome analysis notdone

Fig. 2—Pictures of the fetuses at autopsy. (A) Second fetus (IV-4); (B) first fetus (IV-3)

DISCUSSION

Here, we present a case of familial satellited non-acrocentric chromosome derived from a maternaltranslocation (10;13)(p13;p12) ascertained because offetal abnormalities found at ultrasound.

The phenotypes resulting from the segregation ofthis maternal translocation are pure monosomy 10p13and trisomy 10p13. The trisomy 10p phenotype is nowwell delineated as about 50 cases including a smallnumber of prenatal observations have been reported inthe literature and reviewed by Kozma and Meck(1994). Patients present themselves with osteo-articular

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284 . .

Fig. 3—Partial karyotype of the family. Chromosomes 10 are alwaysrepresented on the left and chromosomes 13 on the right. Theabnormal chromosomes are shown with an arrow. (A) Partialkaryotype of the first fetus (IV-3) with RHG and GTG banding. (B)Partial karyotype of the mother (III-2) with RHG, NOR, GTG andRBG banding

Fig. 4—FISH studies with a subtelomeric probe of chromosome 10p(CTBQ 14 15, locus 10p15). (A) Fetus 1 (IV-3). Only one signal isseen on chromosome 10p confirming the monosomy 10p resultingfrom the segregation of the maternal balanced translocation. (B)Mother (III-2). Two signals are seen, one on chromosome 10p andone on chromosome 13p confirming the presence of a balanced(10;13) translocation. (C) Fetus 2 (IV-4). Three signals are seen; twosignals on chromosome 10p and one signal on chromosome 13pconfirming the trisomy 10p resulting from the segregation of thematernal balanced translocation

and craniofacial abnormalities, growth retardation andsevere psychomotor retardation. Visceral, mainly car-diac, genital and kidney malformations and early deathoccur in one-third of the cases. In the majority of caseshowever, trisomy 10p results from the segregation of aparental translocation and the trisomy is thereforeassociated with a monosomy for another chromosome(Hon et al., 1995). In these cases, clinical features oftrisomy 10p are somewhat confounded with the clinicalfeatures of the associated monosomy. Here, the pheno-type of the fetus IV-4 is compatible with trisomy 10p asseveral features, including growth retardation and limbabnormalities, are observed.

Monosomy 10p13 is associated with facial dysmor-phism, cardiac malformations, genito-urinary abnor-malities and moderate mental retardation. One-third ofreported cases of monosomy 10p13 may present with

Copyright ? 1999 John Wiley & Sons, Ltd.

clinical features reminiscent of DiGeorge syndrome(Monaco et al., 1991). Conversely to trisomy 10p, thevast majority of cases of monosomy 10p results fromde novo deletions and only its postnatal phenotype iswell delineated (Shapira et al., 1994).

A review of 13 prenatally reported observations ofsatellited non-acrocentric chromosomes, the presentreport and two personal unpublished cases are sum-marized in Table 1. Uninformative cases were excludedfrom the study.

In 12/16 cases, the pregnancy went to term andresulted in a normal birth. The chromosome abnor-mality was ascertained because of maternal age (10cases), abnormal maternal serum alpha-fetoprotein(one case) and intra-uterine growth retardation (onecase). One case inherited an apparently balanced trans-location (Arn et al., 1995) and 11 cases inherited the

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Table 1—Review of renatally

Indication forcytogenetic analysis

aryotype ofthe parent Outcome References

Maternal age 1ps N Habibian et al. (1994)2ps N Elliott and Barnes (1992)2qs N Lamb et al. (1995) (two cases)4qs N Miller et al. (1995)4qs N Shah et al. (1997)4qs N Arn et al. (1995)10qs N O’Malley et al. (1997)17ps N Killos et al. (1997)t(4;21)(p16.3;p11.2) N Arn et al. (1995)t(4;?)(q35;p) Abnormal Babu et al. (1987)

Parental translocatio t(5;13)(q13;p12) Abnormal (TOP) Dev et al. (1979)Ultrasound abnorma 14qs Normal at age three Personal case

4qs Abnormal Mihelick et al. (1984)t(10;13)(p13;p12) Abnormal (TOP) Present case

Abnormal maternal 4qs N Personal case

N: normal; TOP: term

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the cases of satellited non-acrocentric chromosomes ascertained p

Karyotype ofthe proband

K

46,XX,1pspat 46,XY,2psmat 46,XX,2qsmat 46,XX,46,XX,4qsmat 46,XX,4qsmat 46,XX,47,XYY,4qtermat 46,XX,46,XX,10qspat 46,XY,46,XX,17pspat 46,XY,46,XY,t(4;21)(p16.3;p11.2)pat 46,XY,46,XY,del(4q35)t(4;?)(q35;p)pat 46,XY,

n 46,XX,der(5)t(5;13)(q13;p12)mat 46,XX,lities 46,XY,14qspat 46,XY,

46,XY,4qspat 46,XY,46,XX,der(10)t(10;13)(p13;p12)mat 46,XX,

AFP 46,XY,4qspat 46,XY,

ination of pregnancy.

286 . .

same satellited chromosome carried by one of theparents. In these cases, the satellited chromosomederived presumably from a familial translocationinvolving the short arm of an acrocentric chromosomeand resulting only in a small loss of genetic materialfrom the non-acrocentric chromosome. Finally, thecase ascertained by intra-uterine growth retardation isnormal at age three but no information is available forthe other cases.

In 4/16 cases, the pregnancy was interrupted and anabnormal phenotype was found at autopsy. Here,prenatal diagnosis was indicated because of a knownmaternal balanced translocation (one case) (Dev et al.,1979), advanced maternal age (one case) (Babu et al.,1987), and abnormal findings at ultrasound (two cases)(present case; Mihelick et al., 1984). Two cases inher-ited an unbalanced product resulting from the segre-gation of a parental translocation (present case; Dev etal., 1979). One case resulted in an abnormal phenotypedue to a de novo deletion involving the paternal satel-lited chromosome (Babu et al., 1987). Finally, onefetus inherited the same parental satellited chromo-some but had an abnormal phenotype (Mihelick et al.,1984). It is important to consider that in this particularcase, no FISH study was performed.

Interestingly, chromosome 4q is frequently observedas a satellited chromosome (6/16 in the present study).

After reviewing the 16 prenatal cases of satellitedchromosomes and after excluding the three cases wherethe cause of the abnormal phenotype of the offspring isobvious (Babu et al., 1987; Dev et al., 1979; presentcase), an abnormal phenotype is observed in 1/13 cases(7·6 per cent). Indeed, in that case with craniorachis-chisis, a phenotypically abnormal offspring inheriteda parental satellited chromosome present in a pheno-typically normal parent. Unfortunately, the molecularbasis of this adverse outcome remains unknown and acoincidence association cannot be excluded. Therefore,if an additional risk exists, it should be small, but infamilies with a phenotypically abnormal offspringinheriting a rearrangement present in one of the nor-mal parents, detailed FISH and molecular studiesmight be required to confirm the balanced structural orfunctional nature of the rearrangement.

In conclusion, here we report on the prenatal diag-nosis of a new case of translocation resulting in asatellited non-acrocentric chromosome. The prenataldiagnosis of such a chromosome rearrangementimplies a detailed cytogenetic analysis of the familyincluding a standard solid giemsa stain, severalbanding techniques and FISH using subtelomericprobes.

We would like to thank T. Meitinger for providing uswith the probe CTBQ 14 15, M. Prieur for criticalreading of the manuscript and J. Rapicault for herexcellent technical work.

Copyright ? 1999 John Wiley & Sons, Ltd.

REFERENCES

Arn, P.H., Younie, L., Russo, L., Zackowski, J.L.,Mankinen, C., Estabrooks, L. (1996). Reproductive out-come in 3 families with a satellited chromosome 4 withreview of literature, Am. J. Med. Genet., 57, 420–424.

Babu, V.R., Roberson, J.R., Van Dyke, D.L., Weiss, L.(1987). Interstitial deletion of 4q35 in a familial satellited4q in a child with developmental delay, Am. J. Hum.Genet., 41 (Suppl.), A113.

Dev, V.G., Byrne, J., Bunch, G. (1979). Partial translocationof NOR and its activity in a balanced carrier and hercri-du-chat fetus, Hum Genet., 51, 121–136.

Elliott, J., Barnes, I.C.S. (1992). A satellited chromosome 2detected at prenatal diagnosis, J. Med. Genet., 29, 203.

Estabrooks, L.L., Lamb, A.N., Kirkman, H.N., Callanan,N.P., Rao, K.W. (1992). A molecular deletion of distalchromosome 4p in two families with a satellited chromo-some 4 lacking the Wolf–Hirschhorn syndrome phenotype,Am. J. Hum. Genet., 51, 971–978.

Habibian, R., Hajianpour, M.J., Shaffer, L.G., Niedenard,L., Hajianpour, A.K. (1994). Genotype–phenotype corre-lation in satellited 1p chromosome: importance of fluor-escence in situ hybridization (FISH) applications, Am. J.Hum. Genet., 55 (Suppl.), A106.

Hon, E., Chapman, C., Gun, T.R. (1995). Family withpartial monosomy 10p and trisomy 10p, Am. J. Med.Genet., 56, 136–140.

Killos, L.D., Lese, C.M., Mills, P.L., Precht, K.S., Stanley,W.S., Ledbetter, D.H. (1997). A satellited 17p with telo-mere deleted and no apparent clinical consequence, Am. J.Hum. Genet., 61 (Suppl.), A130.

Kozma, C., Meck, J.M. (1994). Familial trisomy 10p result-ing from a maternal pericentric inversion, Am. J. Med.Genet., 49, 281–287.

Lamb, A.N., Pettanati, M., Hanna, J., Krasikov, N., Neu,R., Rao, N., Weinstein, M., Weiser, J., Estabrooks, L.(1995). Six cases of satellited long arm of chromosome 2detected during prenatal chromosome diagnosis, Am. J.Hum. Genet., 57 (Suppl.), A282.

Mihelick, K., Jackson-Cook, C., Hays, P., Flannery, D.B.,Brown, J.A. (1984). Craniorachischisis in a fetus withfamilial satellited 4q, Am. J. Hum. Genet., 36 (Suppl.),105S.

Miller, I., Songster, G., Fontana, S., Hsieh, C. (1995).Satellited 4q identified in amniotic fluid cells, Am. J. Med.Genet., 55, 237–239.

Monaco, G., Pignata, C., Rossi, E., Marscellaro, O.,Cocozza, S., Ciccimara, F. (1991). DiGeorge anomalyassociated with 10p deletion, Am. J. Med. Genet., 39,215–216.

O’Malley, D.P., Diehn, T., Bullard, B., Netzloff, M.L., VanDyke, D.L., Feldman, G.L., Ledbetter, D., Lese, C.,Precht, K., Storto, P. (1997). Satellite chromosome 10detected prenatally in fetus and mosaic in a parent, Am. J.Hum. Genet., 65 (Suppl.), A159.

Shah, H.O., Verma, R.S., Conte, R.A., Chester, M.,Shklovskaya, T.V., Kleyman, S.M., Diaz-Barrios, V.,Feldman, B., Lin, J.H., Sherman, J. (1997). Fishing fororigin of satellite on the long arm of chromosome 4, Am. J.Hum. Genet., 61 (Suppl.), A375.

Shapira, M., Borochowitz, Z., Bar-El, H., Dar, H., Etzioni,A., Lorber, A. (1994). Deletion of the short arm ofchromosome 10 (10p13): report of a patient and review,Am. J. Med. Genet., 52, 34–38.

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