PRENATAL DIAGNOSISPrenat Diagn 2005; 25: 292–295.Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/pd.1105

CASE REPORT

Prenatal foetal diagnosis of partial trisomy 3q andmonosomy 13p due to a maternal balanced rearrangement

Antonio Pires1, Lina Ramos2, Margarida Venancio2, Ana Isabel Rei3, Sergio Castedo4 and Jorge Saraiva2*1Department of Paediatric Cardiology, Hospital Pediatrico de Coimbra, Portugal2Department of Medical Genetics, Hospital Pediatrico de Coimbra, Portugal3Prenatal Diagnosis Unit, Maternidade Bissaya Barreto, Coimbra, Portugal4GDPN, Genetica Medica e Diagnostico Pre-Natal, Porto, Portugal

The authors describe a case of a male foetus whose ultrasound at 20 weeks’ gestation revealed cystichygroma, cleft lip and ventricular septal defect. Amniotic fluid cytogenetics using GTG banding showeda 46,XY,der(13)t(3;13)(q12;p11.1) rearrangement, and fluorescence in situ hybridization (FISH) delineated therelevant breakpoints. Familial studies identified a maternal balanced translocation involving chromosomes 3and 13. The post-mortem examination confirmed the prenatal ultrasound findings. Copyright 2005 JohnWiley & Sons, Ltd.

KEY WORDS: trisomy 3q12; cystic hygroma; cleft lip; ventricular septal defect; short long bones

INTRODUCTION

Full trisomy 3 is incompatible with life and is present inabout 1% of karyotyped spontaneous abortions (Mon-tero et al., 1988). Partial trisomy 3, however, can beviable, depending on the size of the chromosomal seg-ment involved. There are several reports of post-nataldetection of partial trisomy of 3p and 3q (Schinzel,2001). Partial trisomy of chromosome 3 is in 60% ofthe cases a result of malsegregation of parental bal-anced translocations involving that chromosome withde novo duplications being less common (Conte et al.,1995; Tranebjaerg et al., 1987). In a review of 40 casesof 3q duplication (Steinbach et al., 1981), only 10 rep-resented de novo 3q duplications. Phenotypically, thedistal dup (3q) syndrome (mental and growth retarda-tion, hirsutism, synophrys, broad nasal root, antevertednares, downturned corners of the mouth, malformed ears,palate, renal and cardiac anomalies) partially overlapswith the Brachmann-de-Lange syndrome, suggesting anas yet unproven molecular relationship between thesetwo syndromes (Aqua et al., 1995). Most cases sharesimilar clinical features regardless of other associatedchromosomal imbalances, underlying the importance ofthe duplicated 3q segment (Tranebjaerg et al., 1987).Survival is related to the underlying malformations, par-ticularly cardiac defects, with the majority dying in earlyinfancy (Tranebjaerg et al., 1987). Severe mental andgrowth retardation are usually diagnosed early in thosethat survive the first year of life (64%) (Wilson et al.,1985).

*Correspondence to: Jorge Saraiva, Servico de Genetica Medica,Hospital Pediatrico de Coimbra, Av. Bissaya Barreto, 3000-075Coimbra, Portugal. E-mail: j.saraiva@hpc.chc.min-saude.pt

CASE REPORT

A 26-year old, healthy, primigravida presented at13 weeks’ gestation for routine foetal ultrasonography.Her partner was 32 years old, also healthy, and thecouple was non-consanguineous. The pregnancy wasplanned and there was no past history of irradiation ordrug exposure. Family history revealed that the patient’smother had two previous spontaneous abortions as wellas an early neonatal death of a child with reported mul-tiple abnormalities, none of which was documented.Neither chromosomal analysis nor post-mortem exam-inations of the foetuses and the newborn were under-taken. Concurrently, her sibling was pregnant with anapparently healthy foetus.

Up to the first ultrasound examination, the pregnancywas considered uneventful.

The foetal ultrasound revealed partial vermal agene-sis, micrognathia, cystic hygroma of the neck, cleft lip,shortening of the long bones (<2SD) and ventricularseptal defect (VSD). The remaining biometric measure-ments were consistent with the gestational age. Theplacenta and umbilical cord were normal, as was theamniotic fluid volume. Amniocentesis was carried out,and cytogenetic analysis by GTG banding showed a46,XY,der(13)t(3;13)(q12;p11.1) karyotype (Figure 1),which was confirmed by fluorescence in situ hybridiza-tion (FISH). Peripheral blood from the mother wasalso karyotyped and a balanced reciprocal translocationfound [(46,XX,t(3;13)(q12;p11.1)] (Figure 2). It was notpossible to study other maternal family members, norwere we able to investigate the father.

The pregnancy was medically terminated at 23 weeks’gestation. A 600-g male foetus was born with severalexternal anomalies, namely, cystic hygroma of the neck,cleft lip, broad thumb and shortening of the long bones

Copyright 2005 John Wiley & Sons, Ltd. Received: 29 June 2004Revised: 17 December 2004

Accepted: 22 December 2004

PRENATAL FOETAL DIAGNOSIS OF PARTIAL TRISOMY 3Q AND MONOSOMY 13P 293

Figure 1—Foetus derivative chromosome 13, der(13)t(3;13)(q12;p11.1) and illustration of normal chromosomes 3 and 13 (left) andof the derivative (13)t(3;13)(q12;p11.1) (right) with arrows showingthe breakpoints

(Figure 3), also documented by X-ray films (Figure 4).These also showed partial absence of the skull (Figure 5)and short first metacarpals and bifid distal phalanges ofboth thumbs (Figure 6).

DISCUSSION

This appears to be the first case of partial trisomy 3qreported in the literature derived from unbalanced seg-regation of a maternal translocation involving the longarm of chromosome 3 and the short arm of chromo-some 13. On the basis of the past obstetric history onthe maternal side, namely, the proband’s grandmother, amaternally inherited chromosomal aberration was likely.

Although this is a double segment imbalance, thefeatures found in this foetus are due to the partialduplication of the long arm of chromosome 3 as thedeletion of the short arm of the acrocentric chromosome13 has no consequence. Most of the reported casesof partial trisomy 3q involve the 3q21-qter and 3q25-qter segments. In our case, however, the translocated

Figure 3—23-week foetus with right cleft lip, hypertelorism andbroad thumb

segment (3q12) was more proximal and hence larger.Interestingly, as reported in the literature, there does notappear to exist a direct relationship between the length

Figure 2—Maternal chromosomes 3 and 13 showing the t(3;13)(q12;p11.1) balanced reciprocal translocation with schematic illustration of normalchromosomes 3 and 13 (left) and of the derivative chromosomes 3 and 13 (right)

Copyright 2005 John Wiley & Sons, Ltd. Prenat Diagn 2005; 25: 292–295.

294 A. PIRES ET AL.

Figure 4—Foetal trunk and limbs X-ray with shortening of long bones

Figure 5—Skull X ray with posterior ossification defect

of the trisomic segment and the clinical expressionor outcome. Indeed, it seems that duplication of the3q25-qter region would suffice to cause the typicalfacies found in this syndrome (Wilson et al., 1985). Theclinical manifestations of 44 cases of newborns with

Figure 6—Foetal hand X rays with bilateral short first metacarpalsand bifid distal phalanges of the thumbs

Table 1—Clinical manifestations of the dup(3q) syndrome

Feature % Our case

Female sex 58 MaleDeath before 12 months 36 Foetal deathHypertrichosis 86 −Abnormal head shape 92 +Upslanting palpebral fissures 56 +Broad nasal root 100 +Anteverted nares 91 +Long upper lip 85 −Maxillary prognathia 86 MicrognathiaDownturned corners of themouth

82 −High arched palate 100 −Cleft palate 79 Cleft lipMalformed auricles 94 −Short or webbed neck 93 Cystic hygromaAbnormal chest 89 −Cardiac defects 75 Ventricular septal

defectOmphalocoele 23 −Renal or urinary tractanomalies

48 −Genital abnormalities 61 −Clinodactyly 90 −Hypoplastic nails 64 −Simian crease 74 −Talipes 64 −Other skeletal anomalies 66 +Brain anomalies/seizures 83 +Modified from the table in the review by Wilson GD, Dasouki M,Barr M 1985 Further delineation of the dup(3q) syndrome. Am J MedGenet 22: 117–123.

the dup (3q) syndrome are shown in Table 1. As ourcase was a 23-week-old foetus, the majority of thesewere not evident. Cardiac malformations are commonlyfound in partial trisomy 3q21, but absent from partialtrisomy 3q25 or more distal (Montero et al., 1988).Hence, based on these findings, one could speculatethat genes related to foetal cardiac development are alsolocated in the more proximal segments of the long armof chromosome 3. The short arm of chromosome 3 alsoappears to be rather important in cardiac development,as 84% of patients with partial trisomy 3p syndromehave congenital heart problems (Reiss et al., 1986).

Copyright 2005 John Wiley & Sons, Ltd. Prenat Diagn 2005; 25: 292–295.

PRENATAL FOETAL DIAGNOSIS OF PARTIAL TRISOMY 3Q AND MONOSOMY 13P 295

Cystic hygromata are well-known ultrasonographicclues for the screening of many genetic conditions, suchas Turner’s syndrome and trisomies 13, 18 and 21.This feature has also been reported in other imbalances,namely, partial trisomy 3qter and monosomy 6q (Chen,2001), suggesting that, when diagnosed, other chromo-somal abnormalities might be implicated. Another inter-esting finding in our case was the presence of shorteningof the long bones, which to our knowledge is a charac-teristic previously not described in published cases ofpartial trisomy 3q, but found in a case of monosomy 3p(Chen et al., 1996).

The cytogenetic diagnosis permitted appropriate gene-tic counselling, not only related to the ongoing preg-nancy but also offering the possibility of prenatal diag-nosis in future pregnancies, as the recurrence risk for awoman with a t(3;13) balanced reciprocal translocationis 16.31% (with a confidence interval of 95%) accordingto the HC Forum (http://hcforum.imag.fr/).

REFERENCES

Aqua MS, Rizzu P, Lindsay EA, et al. 1995. Duplication 3psyndrome: a molecular delineation of the critical region. Am J MedGenet 55(1): 33–37.

Chen CP. 2001. Prenatal diagnosis of partial trisomy 3q(3q22-qter)and monosomy 6q(6q25.3-qter) in a fetus with sonographic findingsof cystic hygromata colli and unilateral pleural effusion. PrenatDiagn 21(1): 73.

Chen CP, Fen-Fen L, Sheau-Wen J, Chen-Li L, Chung-Chi L. 1996.Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p infetuses with holoprosencephaly. Clin Genet 50: 321–326.

Conte RA, Pitter JH, Verma RS. 1995. Molecular characterization oftrisomic 3p24.1-3pter: a case with review of the literature. ClinGenet 48(1): 49–53.

Montero MR, Martinez A, Fayos JL, Alvarez V. 1988. A new case ofpartial trisomy 3 (q25-qter) in a newborn. Ann Genet 31(1): 65–68.

Reiss JA, Sheffield LJ, Sutherland GR. 1986. Partial trisomy 3psyndrome. Clin Genet 30: 50–58.

Schinzel A. 2001. Catalogue of Unbalanced Chromosome Aberrationsin Man (2nd edn), Walter de Gruyter: Berlin, New York.

Steinbach P, Adkins WN Jr, Caspar H, et al. 1981. The dup(3q)syndrome: Report of eight cases and review of the literature. Am JMed Genet 10: 159–177.

Tranebjaerg L, Baekmark UB, Dyhr-Nielsen M, Kreiborg S. 1987.Partial trisomy 3q syndrome inherited from familial t(3;9)(q26.1;p23). Clin Genet 32(2): 137–143.

Wilson GD, Dasouki M, Barr M. 1985. Further delineation of thedup(3q) syndrome. Am J Med Genet 22: 117–123.

Copyright 2005 John Wiley & Sons, Ltd. Prenat Diagn 2005; 25: 292–295.