J. Perinat. Med. 38 (2010) 565–566 • Copyright � by Walter de Gruyter • Berlin • New York. DOI 10.1515/JPM.2010.075

2010/203

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Letter to the editor

Double aneuploidy of trisomy 18 and Klinefelter syndrome:

prenatal diagnosis and perinatal outcome

Figure 1 Shows depressed anterior wall of the chest – pectusexcavatum.

Muzibunnisa Begam1, Gharid N. Bekdache1, SabitaK. Murthy3 and Hisham M. Mirghani1,2,*1 Department of Obstetrics and Gynecology, Fetal Medicine

Unit, Tawam Hospital, Al Ain, United Arab Emirates2 Department of Obstetrics and Gynecology, Faculty of

Medicine and Health Sciences, United Arab EmiratesUniversity, Al Ain, United Arab Emirates

3 Genetics Center, Al Wasl Hospital, DOHMS, Dubai,United Arab Emirates

Sir,The presence of double aneuploidy in the same individual

is a rare phenomenon since they usually involve at least onelethal aneuploidy and end in early miscarriage. Although tri-somy 18 (Edward syndrome) and Klinefelter syndrome arerelatively common aneuploidies, with an incidence of 1:1000and 1:600, respectively, they very rarely co-exist in oneindividual.

We present a case of a rare combination of trisomy 18 andXXY diagnosed at 34 weeks’ gestation. Ultrasound exami-nation showed several markers of chromosomal anomalies:choroid plexus cyst, severe asymmetrical intrauterine growthrestriction (IUGR), strawberry shaped head, micrognathia,cerebellar hypoplasia, membranous ventricular septal defect,bilateral club feet, and clinodactyly. In addition, there waspectus excavatum (Figure 1). Amniocentesis and cytogeneticanalysis revealed double aneuploidy of both trisomy 18 andKlinefelter syndrome, 48, XXYq18 (Figure 2). The babydied on the second postnatal day. The parents declinedautopsy.

*Corresponding author:Dr. Hisham M. Mirghani, FRCOGDepartment of Obstetrics and GynecologyFaculty of Medicine and Health SciencesUnited Arab Emirates UniversityPO Box 17666Al-AinUnited Arab Emirates (UAE)Tel.: q971 3 7137562Fax: q971 3 7672067E-mail: hmirghani@uaeu.ac.ae

A total of nine case reports, including our case, describedthe combination of trisomy 18 and Klinefelter syndromew1–8x. The mean maternal age at diagnosis was31.4"9.8 years. The mean gestational age at delivery was39.5"2.4 weeks. Of the nine cases, only two (22.2%) werediagnosed prenatally. The majority of reported features weremainly related to trisomy 18. All nine (100%) neonates hadmicrognathia, eight (88.9%) were growth restricted and sev-en (77.8%) had cardiac anomalies. Features related to Kli-nefelter syndrome were minimal. Four (44.4%) hadclinodactyly. However, prenatal diagnosis of pectus excava-tum was only reported in our case. There was great variationin neonatal survival, with a mean of 101.8"159.4 days.However, when the exceptional longest survival()15 months) was excluded the mean number of days ofpostnatal survival was 43.8"47.2 days.

The cytogenetics of double aneuploidy is unclear. It issuggested that the majority results from two non-disjunctionsin gametogenesis or a single non-disjunction in a trisomiczygote. However, we were unable to observe a strong asso-ciation between maternal age and double aneuploidy (triso-my 18 and XXY) in our review.

Given the rarity of double aneuploidy and scant publisheddata, the incidence and recurrence risk are difficult to estab-lish. Therefore, genetic counseling is challenging. Neverthe-less, the prognosis for 48, XXYq18 patients remains verypoor and invariably lethal. Surprisingly, one infant wasreported as living beyond 15 months of age w6x.

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566 Begam et al., Double aneuploidy of trisomy 18 and Klinefelter syndrome

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Figure 2 Shows karyotype characteristic double aneuploidy of trisomy 18, an extra X sex and 18th chromosome.

References

w1x Al-Awadi SA, Al-Naggar RL, Tayel SM, Uma R. Double aneu-ploidy: 48, XXYq18 in a bedouin boy. Med Princ Pract. 1999;8:241–4.

w2x Bach C, Toublanc JE, Gautier M. Case of double aneuploidy:trisomy 18 and XXY. Ann Genet. 1973;16:61–6.

w3x Cohen MM, Bumbalo TS. Double aneuploidy: trisomy-18 andKlinefelter syndrome. Am J Dis Child. 1967;113:483–6.

w4x Haylock J, Fitzgerald M, Danks D, Dennet X. Two cases ofthe 18 trisomy syndrome, one in combination with an XXYkaryotype. Hum Chromos Newsl. 1963;9:15–6.

w5x Henchman DC, Grey J, Campbell JB, Nance S. Klinefelter syn-drome with mosaicism trisomy-18. Aust Paediatr J. 1970;6:142–5.

w6x Jia-Woei Hou. Double aneuploidy: trisomy 18 and XXY in aboy. Chang Gung Med J. 2006;29:6–12.

w7x Komwilaisak R, Ratanasiri T, Komwilaisak P, Luengwattana-wanit S. Three-dimensional ultrasonographic findings of therare chromosomal abnormality 48, XXY/q18: a case report. JMed Assoc Thai. 2004;87:198–203.

w8x Nielsen J, Vetner M, Holm V, Askjaer AS, Reske-Nielsen E,Zizka J. Klinefelter syndrome and trisomy 18 in a newbornboy. Clin Genet. 1978;13:259–64.

The authors stated that there are no conflicts of interest regardingthe publication of this article.

Received November 8, 2009. Revised February 7, 2010. AcceptedFebruary 22, 2010. Previously published online May 5, 2010.

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