Portal de Periódicos da CAPES

Double trisomy

2003; Wiley; Volume: 124A; Issue: 1 Linguagem: Inglês

10.1002/ajmg.a.20340

1552-4833

Shibo Li, Susan J. Hassed, John J. Mulvihill, Ambika K. Nair, Deborah J. Hopcus,

Prenatal Screening and Diagnostics

Three years after the discovery of the correct number of chromosomes in a normal human being, Ford et al. reported the first case with double trisomy [Ford et al., 1959]. The paper described a patient with clinical phenotypes of both mongolism (Down syndrome) and Klinefelter syndrome (48,XXY, + 21). Uchida and Bowman [1961] reported the first double trisomy case 48,XXX, + 18. Since then, a total of 16 cases have been reported [Ricci and Borgatti, 1963; Haas and Lewis, 1966; Engel et al., 1967; Taylor, 1968; Emberger et al., 1971; Madahar et al., 1974; Verma and Dosik, 1980; Rosenfeld et al., 1981; Sonoda et al., 1985; Imai et al., 1987; Sonoda et al., 1987; Jaruratanasirikul and Jinorose, 1994; Moore et al., 1994; Tsukahara et al., 1994; Chen et al., 2000]. One of the patients was a mosaic [Engel et al., 1967]. As expected, most of the patients with 48,XXX, + 18 died in an early postnatal period, the longest published survival of a 48,XXX, + 18 patient was 12 months, the patient was alive at the time of diagnosis [Jaruratanasirikul and Jinorose, 1994]. In one case, molecular genetic analysis using polymorphic DNA markers revealed that the patient inherited two copies of a single maternal allele in chromosome 18 and chromosome X, indicating that double non-disjunction occurred in maternal meiosis II [Chen et al., 2000]. Here we present another patient who had a double trisomy of X chromosome and chromosome number 18 (48,XXX, + 18). Prenatally, the patient was identified to have intrauterine growth retardation. She was born at term following induction of labor. Apgar scores were 2 and 7 and birth weight was 1,762 g. There was a left cephalohematoma. Ears were lowset and posteriorly rotated. There was a subconjunctival hemorrhage in the left eye. The palate was not visualized due to intubation and the sternum was short. There were hypoplastic labia majora, a large clitoris, prolapsed cervix, and an anteriorly placed anus. Fingers were overlapping with dystrophic nails, ulnar deviation, and camptodactyly. Toenails were hypoplastic, and there were prominent heels bilaterally. A patent ductus arteriosus was repaired. The family history was negative for previous children with anomalies and there were no known pregnancy losses. Chromosome analysis was requested which revealed an abnormal female karyotype of 48,XXX, + 18. The patient died at 14 days of age. The patient showed the classical signs of trisomy 18: low set malformed ears, short sternum, overlapping fingers with hypoplastic nails, prominent heels, heart defect, and short life span. None of these features was contributed by the extra chromosome X, since triple-X female is phenotypically normal. In a review of the literature, we found 16 cases with 48,XXX, + 18 reported so far. Maternal origin of extra X and 18 was determined in one case by using the polymorphic DNA markers from chromosomes X and 18 [Chen et al., 2000]. Rosenfeld et al. [1981] and Imai et al. [1987], reviewing their case as well as five cases in the literature, observed that malformations in the hands, ears, and kidneys showed significantly higher frequency on the right side. Although the reasons for this phenomenon were not clear, they felt that right-sided malformations might indicate the possibility of 48,XXX, + 18. In our case, cephalohematoma and subconjunctival hemorrhage were noted on the left side. More cases are required before a conclusion can be made. Various combinations of double trisomy in more than four-dozen liveborn cases have been described in the literature. Some combinations are more common than others (Table I). There seems to be no report of 48,XXX, + 13, and only one case each of 48,XYY, + 13 and 48,XYY, + 18. The common double trisomies were the combinations of 48,XXY, + 21 and 48,XXX, + 18; 20 and 16 cases were reported, respectively. This may imply that individuals with double trisomies, 48,XXY, + 21 and 48,XXX, + 18, just like patients with Down's syndrome and trisomy 18, are more compatible with life. It also could be that cases of other combined trisomies exist but have not been published. Chen et al. [2000], Emberger et al. [1971], Engel et al. [1967], Haas and Lewis [1966], Imai et al. [1987], Jaruratanasirikul and Jinorose [1994], Madahar et al. [1974], Moore et al. [1994], Ricci and Borgatti [1963], Rosenfeld et al. [1981], Sonoda et al. [1985], Sonoda et al. [1987], Taylor [1968], Tsukahara et al. [1994], Uchida and Bowman [1961], Verma and Dosik [1980] Al-Awadi et al. [1990], Amendares and Buentello [1990], Day et al. [1963], Gobbi et al. [1980] Ebbin et al. [1972], Malhes et al. [1977] Cohen and Bumbalo [1967], Nielsen et al. [1978], van Ravenswaaij-Arts et al. [1997] Buchanan [1975], Court-Brown et al. [1964], Erdtmann et al. [1971], Ford et al. [1959], Gelderen and Hustinx [1961], Grouchy et al. [1965], Hamerton et al. [1962], Hecht et al. [1969], Hou and Wang [1996], Hustinx et al. [1961], Lanman et al. [1960], Lehmann and Forssman [1960], Lorda-Sanchez et al. [1991], Maximilian et al. [1980], Milcus and Maicanesco [1963], Pfeiffer [1964], Saura et al. [1983], Schmidt et al. [1978], Tuck et al. [1983], Turpin et al. [1964] Crolla and Machin [1980] Felding and Kristoffersson [1981] Leary [1975], Murken et al. [1972], Mutchinick and Matayoshi [1980], Neu et al. [1971], Schwanitz and Hagner [1978], Stoll et al. [1976], Teramoto et al. [1985], Townsend [1982] Grosse and Schwanitz [1977] Sulewski et al. [1980] Barnett et al. [1987] Kardon et al. [1980] Webb et al. [1984] Casey et al. [1981], Ong and Robertson [1995] It is apparent that double trisomy is extremely rare in liveborns. These small portion of double trisomies presented here may well represent a tip of the iceburg in the reproductive population; the majority of double trisomies and trisomy 18 may end in spontaneous abortion, noticed or unnoticed. On the other hand, it is not clear what percentage of trisomy 18 or double trisomy pregnancies has been rescued and the percentage of those pregnancies that end in uniparental disomy (UPD).