REPORT OF A NEW CASE WITH PENTASOMY X AND NOVEL CLINICAL FINDINGS
Demirhan O, Tanriverdi N, Yilmaz MB, Kocaturk-Sel S, Inandiklioglu N, Luleyap U, Akbal E, Comertpay G,Tufan T, Dur O
*Corresponding Author: Professor Dr. Osman Demirhan, Department of Medical Biology and Genetics, Faculty of Medicine, Çukurova University, 01330 Saricam, Adana, Turkey. Tel: +90-322-338-7140. Fax: +90-322- 338-6572. E-mail: osdemir@cu.edu.tr
page: 85

DISCUSSION

Pentasomy X is a rare chromosomal abnormality with an unknown prevalence, and has been associated with severe clinical conditions. Pentasomy X syndrome was first reported by Kesaree and Wooley in 1963 [1]. These patients usually have normal genitalia, but secondary sex characteristics can be incomplete. Pentasomy X syndrome has been associated with severe clinical conditions, presumably resulting from failure or disruption of X chromosome inactivation [7]. No adults with pentasomy X have been reported since the prognosis is universally poor. Here, we describe a case of 49,XXXXX karyotype in a 1-year-old girl. The principal features of the pentasomy X syndrome are set out in Table 1 and illustrated in Figure 1. Pentasomy X chromosomes result sporadically from either meiotic non disjunction, where a chromosome fails to separate during the first or second division of gametogenesis, or from mitotic non disjunction in the developing zygote. If by chance the X chromosomes do not separate properly and they go on to the next cell division and again do not divide properly, when the sperm fertilizes the egg the fetus can then end up with four X chromosomes and one X (49,XXXXX). Just as in our study, all the chromosome X-specific STR markers of the case were inherited from the mother (origin of the aneuploidy is maternal) and heterozygosity was retained in all regions (proximal, medial and distal regions) of the four chromosomes. This is the expected conditions of non disjunction in both meiosis I and meiosis II. Some researchers indicate that molecular genetic analyses using polymorphic DNA markers have enabled the study of non disjunction of fetal aneuploidy as well as determination of parental origin and cell stage errors at meiosis I or II [3,5,6]. In the present study, the most important prognostic feature consists of extreme thenar atrophy, hypotonia, micrognathia and cardiovascular anomalies (Figure 1). Some of these clinical manifestations were consistent with those described previously in patients with pentasomy X, except for thenar atrophy. The hands and feet are generally small and camptodactyly, clinodactyly, and radioulnar synostosis are common findings in the pentasomy X syndrome. In addition to these hand findings, we report the first case with extreme thenar atrophy, which was not found in previous cases. A karyotype is therefore mandatory in infants with moderate-to-severe thenar atrophy, in order to exclude polyploidy X chromosome. Girls with a pentasomy X generally have mental retardation, mongoloid face, short neck, simian crease, clinodactyly of the fifth finger and congenital heart disease [7]. Because most patients with pentasomy X syndrome (including ours) have developmental delay, postnatal growth deficiency, epicanthus and a mongoloid slant of facial anomalies and hypotonia, similar to the abnormalities seen in Down’s syndrome, occasional diagnostic problems have also been reported [8] (Figure 1). Because patients can be misdiagnosed as having Down’s syndrome, the correct diagnosis requires cytogenetic analysis. The patients with pentasomy X syndrome have a poor prognosis due to severe cardiac failure and infectious diseases [2,9-12]. Immunoglobulin anomalies and an increased susceptibility to infection have also previously been reported in patients with pentasomy X. Immunoglobulin values in our case had not been tested. However, history of a greatly increased incidence of recurrent infections and fever was found in our case, whereas Boeck et al. [13] described their patient as having a lifelong history of eczema, recurrent pneumonia and staphylococcal abscess. Pneumonia development from early infancy, as seen in our case, has also been described in this syndrome. The normal external genitalia seen in our case have been reported in previous patients, although gonadal dysfunction has been seen in many cases, including a postmortem case [1,14-16]. These findings suggest that despite the normal appearance of the external genitalia, there is an underlying gonadal dysfunction in patients with pentasomy X syndrome. Because our case was an infant, her sexual development and bone maturation remain to be assessed. Growth deficiency was evident in the majority of affected children at the time of birth. Birth weight of our case was unknown. However, she was born by Cesarean section during the 32nd gestational week as a result of premature membrane rupture, and had postnatal growth deficiency and developmental delay; these anomalies have also been described in this syndrome. Her intellectual functions had not been formally tested, but were suspected to be at low-average. Patients with pentasomy X syndrome generally have congenital heart defects; usually patent ductus arteriosus or a ventricular septum defect [1,8,9,11,12,14,16]. Just as documented, cardiac defects were present in nine (45.0%) of 20 children with 49,XXXXX (Table 1). Our case had a surgical operation for cardiac murmurs and patent ductus arteriosus. Reports in the medical literature agree that around 50.0% of girls are born with a heart condition. However, the medical literature includes girls with an innocent heart murmur. The most common defects are holes between the lower chambers of the heart and a condition called persistent ductus arteriosus that is left-over from the way the circulation operates during fetal life. Some cases are born with a more complex heart condition and will need a surgical operation. Three of those children developed congestive heart failure within the first year of life and required surgical ligation of the ductus. A karyotype is therefore mandatory in female newborns with moderate-to-severe hypotonia (including our case), in order to exclude polyploid mosaicism of the X chromosome [17]. Genetic counseling is indicated during subsequent pregnancies. Parents must realize that, apart from somatic areas being affected (facial dysmorphism, skeletal, cardiovascular and gonadal systems), all major areas of development will be affected by the addition of extra X chromosomes. However, an overall prognosis seems impossible due to a substantial variability within all polysomy X groups. In addition, the other structural abnormalities, del(13)(q22-p2) and chtbr(3q), were observed in two cells of our case (Figure 2). This loss of chromosome and chromatid break may affect susceptibility to the progression of the disease. In conclusion, the clinical manifestations observed in our case were consistent with those described previously in patients with pentasomy X. To the best of our knowledge, we are the first to report thenar atrophy in a case with 49,XXXXX. Chromosome karyotyping is generally required in the presence of facial dysmorphism or other somatic abnormalities, to exclude underlying sex chromosomal aneuploidy disorder, such as the 49,XXXXX syndrome. Additional studies about polyploidies are needed to determine the nature of the errors in such cases. Evaluation of exceptional instances of segregation failure may be useful in improving our understanding of the general mechanisms of non disjunction. Molecular techniques could be useful for the pre and postnatal diagnosis of the common aneuploidies and determining its parental origin. These kinds of studies will improve our knowledge about the mechanisms of aneuploidies, and enable appropriate and prompt genetic counseling. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.



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