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Hadadi N. Case Report of Prenatal Diagnosis of Klinefelter Syndrome Based on Ultrasound Screening. SJRM. 2017; 2 (4) :39-42
URL: http://saremjrm.com/article-1-92-en.html
Sarem Fertility & Infertility Research Center (SAFIR), Sarem Women’s Hospital, Tehran, Iran , N_Hadadi@yahoo.com
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Introduction
Over the past 30 years, extensive research has been carried out to detect prenatal complications by appropriate minimally invasive methods [1]. Among these non-invasive methods, ultrasonographic screening of pregnancy occurs without any direct access to the embryo (NT), which has the lowest risk for mother and fetus. One of the most important ultrasound markers that are considered and measured in screening programs is the degree of fetal neck transplantation [2]. This method was first proposed in about 1992 to detect chromosomal abnormalities in the first trimester of pregnancy [1, 3]. Today, for the first trimester screening tests, ACMG standards and related guidelines, maternal blood biochemical tests, including Free b-HCG and PAPP A, are considered [4]. According to the national guidelines for the prevention of embryonic chromosomal abnormalities in Iran, the necessity and importance of using these standards has been specified [5].
Nuchal thickening (NT), which is actually the largest ​​clear area between the skin and the soft tissue on the back of the neck, is measured in the sagittal view when the CRL is between 45 and 84 mm [1, 2, 5- 7]. The best time for NT screening is between 11-13 weeks, which is expected to have a normal NT size from 2-2.6 mm at this time [1, 2, 7]. In the country guidelines for the prevention of embryonic chromosomal abnormalities in Iran, the selected time intervals for each screening stage are determined according to the existing rules regarding the choice of fetal abortion [5]. However, NT's increase in the determination of the risk of various disorders has different definitions [7]. Anatomical anomalies are associated with an increase in the percentile of NT, and the NT border, with a diameter of 3.5 mm, is helpful in determining the risk of chromosomal anomalies in conducting a prenatal consultation [1, 8, 9]. Increased NT is also associated with adverse pregnancy outcomes, including abortion, fetal death, and termination of pregnancy. Although more than 80% of cases are associated with the birth of a healthy baby, but in the cervical curvature, there is a possibility of 79% to 90% of the correct diagnosis and about 5% of the probability of false positive diagnosis [1, 8, 10].
Approximately one-third of the embryos with elevated NT have chromosomal abnormalities such as trisomy 18, 13 and 21, hypoplasia agenesis or dysplasia, osteodystrophy, atresia or small intestine obstruction, gastroschisis, Noonan syndrome, diaphragm anomalies, Klinefelter syndrome, etc. [1, 7, 8, 10]. One of these abnormalities is the Klinefelter syndrome (47 XXY), which is an aneuploidy chromosomal disorder that occurs in men. [11] A person with this abnormality has an additional X chromosome [12, 13]. The prevalence of double aneuploidy rarely occurs, and it was first reported in 1942. Kline felter syndrome is one of these abnormalities, which is due to the addition of X chromosomes, which causes small testicles and growth of the breasts and disturbs spermatogenesis. The incidence of this complication has been reported approximately one in 500 to one in 1,000 pregnancies [14,15]. Of course, according to observations, the incidence of this malformation in women between the ages of 20 and 30 is lower than that of older women, which indicates the role of maternal age in the occurrence of these abnormalities [14]. The diagnosis of these abnormalities is possible by screening in the first three months of pregnancy, but more accurate examination is needed, including chromosomal examinations. Therefore, in order to detect these abnormalities, NT ultrasound, along with biochemical tests, is recommended to ensure positive cases that should be referred to genetic labs for amniocentesis or more genetic investigations.
 According to the country's guidelines for embryo screening, in case of normal screening in the first step, there is no need for a second stage screening, unless there is a specific clinical point of view. In the case of any reported case, if there is a suspicion of high NT, a second stage of screening is performed. Although in both screening programs, the software has calculated a lower risk for the fetus, more studies are done to diagnose anomalies. As a result, the goal of expressing this complication was to express the importance of prenatal diagnosis. With considering the abdnormal reports, in both first and second trimester of pregnancy, screening should focus on the importance of NT and the necessaty of more chromosal investigation.
 
Patient and methods
A 29-year-old woman, at her first pregnancy, referred to the Sarem hospital screening clinic for screening an aneuploidy stage one at 13 weeks of pregnanc in 2 days (GA: 13W + 2d). In the ultrasonography, the results of pregnancy age was 13W and NT=2.91, and in combination with gestational age and biochemical tests, the FMF protocol was subjected to low risk. However, according to software norm that was obtained in Sarem hospital,  NT was in the upper range between 95 and 99 percentile (Table 1).
 
Table 1) Results of the first stage of the screening process (GA=13W+2d)
 
 
In screening for the second phase of this sample, a quad marker test (four tests UE3, AFP, Free b-hCG and Inhibin A) was performed at 16 weeks of gestation, and the risk of Down syndrome and neuromuscular tube disorders were again reported in low-risk areas (Table 2) .
 
Table 2) Results of different stages of the second trimester screening
 
 
According to ultrasound, other parts were normal in terms of anomalies and no other anioploidic markers were observed. In the prenatal consultation, the patient was told about the accuracy of the screening tests. For definitive diagnosis, echocardiography of the embryo was prescribed. Because of the high NT range, according to the data of Iranian patients referring to Sarem Hospital, an amniocentesis test was requested for him. . In the echocardiography results, no cardiac anomalies were reported, but in the analysis of amniotic fluid, the karyotype was reported as XXY47 (klinefelter Syndrome).
 
Discussion
An increase in NT (above 99 per cent of the population or more than 3.5 mm) can be associated with chromosomal aneuploidy disorders, metabolic disorders, genetic syndromes, congenital infections, constructional disorders, and so on. In the aneuploid screening of stage one, based on NT and PAPP-A and Free BHCC, risk determination is performed for common trisomies 13, 18, and 21. Chromosomal analysis is recommended if the NT is greater than 3.5 mm and the percentile is greater than 99% [1].
In a study by Lichtenbelt et al. In 25057 single- pregnancies, there were 225 cases of NT> 3.5. For all samples, chromosomal analysis was performed. There were 103 chromosomal abnormalities, of which 79 cases were trisomies13, 18 and 21, and in 24 cases i.e. 22.3%, chromosomal anomalies were present [16].
In a meta-analysis performed over a year, it was concluded that NT> 3.5 can be associated with submicroscopic abnormalities that can not be detected in the karyotype.
In the case reported, NT was 2.9 mm. Further studies were conducted on the 95-99% percentile based on the population under study. In an ultrasound scan anomaly, NF was 6.5 mm. In the present situation, the scoring system, based on multiple markers found with genetic sonography, can increase the risk of Down syndrome by only increasing NF alone. Since in the present study, the norm marker in the second stage screening risk was located in low risk area for Down syndrome, further chromosomal studies let to detection of Klinefelter anormality due to increased NT and doubt in the presence of anomalies.
 
Conclusion
In an aneuploid screening, only estimates of the risk of common trisomies 13, 18, and 21 are not required; the NT rate should also be considered separately. Increased NT in excess of 99% of the population, or NT> 5.3 mm, has been insisted in all studies and the indication of supplementary tests. In NT> 9.5% cases, chromosomal problems, other than common trisomies and genetic problems, suggest a norm marker in the screening of the second trimester of the fetus and structural disorders, both cardiac and non-cardiac in screening. Prenatal diagnosis of these disorders is effective in the planning and prognosis of future pregnancy. Among these chromosomal abnormalities, the Kline felter syndrome, in the form of the XXY karyotype, is one in 10,000 in boys, and unfortunately it is not possible to diagnose it until puberty that is manifested by hypogonadism. Early diagnosis and hormone replacement therapy can lead to natural maturation in these individuals.
 
Acknowledgements: The case was not found by the authors.
Ethical permissions: The case was not found by the authors.
Conflict of interests: The case was not found by the authors.
Financial support: The case was not found by the authors.
Contribution of authors
Negin Haddadi (First author), all affairs related to the article were made by her (100%).
Article Type: Case Report | Subject: Reproduction
Received: 2016/08/11 | Accepted: 2017/01/9 | Published: 2018/02/20

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