A viable fetus presenting 68,XX[73]/69,XXX[27] triploid mosaicism

A viable fetus presenting 68,XX[73]/69,XXX[27] triploid mosaicism

A.X. Acosta¹, L.C. Peres², L.F. Mazzucatto¹and J.M. Pina-Neto¹

¹Departamento de Genética e Matemática Aplicada à Biologia, Faculdade de Medicina de Ribeirão Preto, USP, 14049-900 Ribeirão Preto, SP, Brasil. Send correspondence to J.M.P.-N.

²Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, USP.

ABSTRACT

Triploidy is common in human pregnancies. It is detected in 1 to 2% of clinically recognized pregnancies and in approximately 15 to 20% of spontaneous abortions produced by chromosome anomalies. We report a premature liveborn girl (30 weeks of gestation) with microcephaly, facial dysmorphism and skeletal abnormalities who died at one day of age due to respiratory failure. The placenta showed partial hydatiform mole. Autopsy revealed no internal malformations. Cytogenetic analysis of 100 metaphases obtained from renal tissue culture revealed a 68,XX[73]/69,XXX[27] karyotype. To our knowledge this is the first report in the literature of 68,XX[73]/69,XXX[27] mosaicism in a liveborn infant.

INTRODUCTION

Triploidy is a common chromosome anomaly detected in 1 to 2% of clinical recognized pregnancies and in approximately 15 to 20% of spontaneous abortions of chromosomal cause. In approximately 5% of cases, an aneuploidy may be associated (Boué et al., 1985). Almost 85% of the cases present molar degeneration, dispermy being the principal cause. Only nine cases of 68,XX triploidy have been described thus far, seven of them in aborted fetuses (Boué et al., 1985; Uchida and Freeman, 1985; Jacobs et al., 1982), one in a 21-week fetus (Kaffe et al., 1989) and one in a full term liveborn (Merlob et al., 1991).

CLINICAL REPORT

A 27-year-old mother, who had previously conceived two normal children, presented pregnancy-induced arterial hypertension and was treated with alpha-methyldopa. Caesarian section was performed at 30 weeks gestation due to maternal hypertension with chronic and acute fetal distress. The liveborn female infant had a birth weight of 1250 g (50th percentile) and her crown-heel length was 38 cm (25th percentile). She was bradycardic, hypotonic and cyanotic, and discharged large amounts of bloody fluid from the upper respiratory tract. She died during the first day of life due to prematurity complications.

Multiple external abnormalities were found at post-mortem examination (Figure 1), including microcephaly (head circumference was 25 cm - well below the 10th percentile) and dysmorphic features. The infant had low-set ears, eye hypertelorism with inner canthus distance of 2.3 cm and outer canthus distance of 5.4 cm (both more than two standard deviations from normal), a beak-like nose with a low nasal bridge, high arched palate, micrognathia, a short neck with excessive skinfolds, short arms, bilateral fixed ulnar contractures of the hands, cutaneous syndactyly between the 2nd and 3rd fingers, bilateral single palmar crease, bilateral clinodactyly and increased space between the 1st and 2nd toes, bilaterally. No malformations of internal organs were found but there was bilateral pneumothorax, hemorrhagic and fleshy lungs, and a hepatic subcapsular hematoma with hemoperitoneum. Subarachnoid and aqueduct hemorrhages were seen in the brain, as well as subependymal cysts, some of them hemorrhagic. Histological examination revealed interstitial emphysema in the lungs, with early hyaline membrane disease and pulmonary hemorrhage.

Figure 1
- A) Frontal view of the patient, showing microcephaly, hypertelorism, a beak-like nose with a low nasal bridge, short neck with excess skinfolds, short arms; B) side view of the patient: note low-set ears and micrognathia; C) skin syndactyly between the 2nd and 3rd fingers and fixed ulnar contracture; D) bilateral increased space between the 1st and 2nd toes.

The placenta (Figure 2) weighed 410 g and measured 15.8 x 12.6 x 1.5 cm. There were poorly delineated cotyledons on the maternal surface and scattered vesicles (clustered in some areas) measuring up to 1.5 cm in diameter. Light microscopy revealed a few hydropic villi with rare capillaries (Figure 2A). The stroma was edematous but cisternal formations were absent. The trophoblastic epithelium was hypoplastic with only occasional areas of hyperplasia. Trophoblastic inclusions were also absent. The villi were small in the nonhydropic areas, showing rare capillaries. Trophoblastic sprouts were common (Figure 2A). The overall characteristics were of a partial hydatiform mole with widespread hypovascularization of villi.

Figure 2
- A) Histological view of the placenta, presenting partial hydatiform mole; B) disk-shaped placenta with scattered vesicles, measuring up to 1.5 cm in diameter. Hematoxylin and eosin, X25.

Cytogenetic analysis (Figure 3) was made of kidney cells since the blood culture was contaminated. The karyotype with G-band preparations (GTG banding) obtained from three different primary cultures was 68,XX[73]/69,XXX[27], i.e., 73 metaphases with 68,XX and 27 with 69,XXX. Analysis (100 metaphases) of the three primary cultures gave similar results, with a predominance of 68,XX.

Figure 3 -
A) G-banded karyotypes 69,XXX, B) 68,XX.

DISCUSSION

The abnormalities (Table I) found in the present patient were mild compared to those reported in the other cases of classic triploidy (Smith, 1988) and 68,XX (Kaffe et al., 1989; Merlob et al., 1991). Chronic and acute fetal distress was probably secondary to the placental insufficiency, in association with pregnancy-induced hypertension. We believe that these abnormalities, taken together with the complications of prematurity, were responsible for the death of the infant at one day of age.

The presence of 68,XX[73]/69,XXX[27] mosaicism suggests that the original zygotic lineage may have been 69,XXX, i.e., acquisition of extra haploid material occurred, followed by the loss of a sex chromosome (anaphase lag) after the first zygotic divisions. This is further supported by the finding of a 68,XX karyotype in many of the metaphases analyzed. In vitro mosaicism was excluded because the three different primary renal cell cultures showed similar results, with a predominance of 68,XX in all of them. Detection of this type of chromosome mosaicism may depend on the number of cells analyzed and on the type of tissue cultivated.

ACKNOWLEDGMENTS

The authors are grateful to the Photographic Service of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. We acknowledge Dr. Gordan M. Vujanic (Department of Pathology, University of Wales, College of Medicine) and Prof. Dr. David De Jong (Department of Genetics, Faculty of Medicine of Ribeirão Preto, USP), for revising the manuscript. We are also grateful for contributions of FAEPA (Fundação de Apoio ao Ensino, Pesquisa e Assistência) of University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. Publication supported by FAPESP.

RESUMO

A triploidia é uma anomalia cromossômica comum encontrada em 1 a 2% das gestações clinicamente reconhecidas e em cerca de 15 a 20% dos abortos espontâneos de causa cromossômica. Em aproximadamente 5% dos casos, uma aneuploidia pode estar também associada (Boué et al., 1985). Descrevemos um recém-nascido do sexo feminino, prematuro (30 semanas de idade gestacional), com microcefalia, dismorfias faciais e alterações de membros, que foi a óbito com 1 dia de vida por insuficiência respiratória. O exame anátomo-patológico da placenta revelou alterações compatíveis com degeneração molar. A necrópsia da criança não evidenciou malformações internas. A análise citogenética de 100 metáfases, obtidas a partir de cultura de tecido renal, evidenciou cariótipo 68,XX[73]/69,XXX[27]. Apenas 9 casos de triploidia 68,XX foram descritos anteriormente, sendo 7 em abortos, 1 em feto de 21 semanas e 1 em recém-nascido a termo. Consideramos que este estudo seja o primeiro da literatura relatando a ocorrência de mosaicismo 69,XXX/68,XX em um recém-nascido vivo. Os autores discutem os achados clínicos e os possíveis mecanismos envolvidos nesta aberração cromossômica.

(Received April 15, 1997)

• Boué, A., Boué, J. and Gropp, A. (1985). Cytogenetics of pregnancy wastage. Adv. Hum. Genet. 14: 1-57.
• Jacobs, P.A., Szulman, A.E., Funkhouser, J., Matsuura, J.S. and Wilson, C.C. (1982). Human triploidy: relationship between parental origin of the additional haploid complement and development of partial hydatiform mole. Ann. Hum. Genet. 46: 223-231.
• Kaffe, S., Eliasen, C. and Wan, L. (1989). A rare case of 68,XX triploidy diagnosed by amniocentesis. Prenatal Diagn. 9: 857-861.
• Merlob, P., Naor, N. and Shohat, M. (1991). Phenotypic expression of the first liveborn 68,XX triploid newborn. J. Med. Genet. 28: 886-887.
• Smith, D.W. (1988). Recognizable Patterns of Human Malformation 4th edn. W.B. Saunders Company, Philadelphia.
• Uchida, I.A. and Freeman, V.C.P. (1985). Triploidy and chromosomes. Am. J. Obstet. Gynecol. 151: 65-69.

Publication Dates

• Publication in this collection
  23 Feb 1999
• Date of issue
  Sept 1998

History

• Received
  15 Apr 1997