Constitutional Chromosomal Abnormalities Research Articles

Conventional Cytogenetic Analysis of Constitutional Abnormalities: A 20-Year Review of Proficiency Test Results From the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee.

The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure competency and proficiency of clinical cytogenetics testing laboratories through proficiency testing programs for various clinical tests offered by such laboratories, including the evaluation of constitutional abnormalities. To review and analyze 20 years of constitutional chromosome analysis proficiency testing results (2003-2022), primarily utilizing G-banded karyograms. A retrospective review of results from 2003 through 2022 was performed, identifying challenges addressing constitutional disorders. The chromosomal abnormalities and overall performance were evaluated. A total of 184 cases from 161 proficiency testing challenges were administered from 2003 through 2022. Challenges consisted of metaphase images and accompanying clinical history for evaluation of numerical and/or structural abnormalities. Of the 184 cases, only 2 (1%) failed to reach an 80% grading consensus for recognition of the abnormality. Both cases illustrated the limitations of correctly characterizing some chromosomal abnormalities, including recombinant chromosomal abnormalities and isochromosome identification. In addition, 2 cases failed to reach a consensus for nomenclature reporting: 1 with an isochromosome and another with a duplication. This 20-year review illustrates the high rate of competency and proficiency of cytogenetic laboratories in the correct identification of constitutional chromosome abnormalities.

Cytogenetic abnormalities associated with reproductive failure in Pakistani population: Experience of a tertiary care hospital.

Constitutional chromosomal abnormalities play a significant role in causing reproductive anomalies in individuals of reproductive age. With the rapid advancement of genome engineering techniques, it has now become possible to cure different genetic disorders. However, very limited data is available regarding the prevalence of such aberrations in the Pakistani population. Considering this factor, this retrospective analysis was undertaken to elucidate the type and prevalence rate of such abnormalities in our population. A total of 241 individuals, who were referred to the Liaquat National Hospital, from January 2017 to December 2021, with a history of infertility or miscarriages, were evaluated using the standard GTG banding technique. The results revealed a notably high percentage 44(18.2%) of chromosomal abnormalities in our population. Surprisingly, the frequency of these anomalies was observed to be higher in males than in females. However, further research is needed using a larger sample size to confirm the findings of this investigation.

Cytogenetic analysis of 3488 patients with recurrent pregnancy loss: An experience of two decades from a tertiary care center in South India

BackgroundRecurrent pregnancy loss (RPL) affects approximately 15–20% of couples. Constitutional chromosomal abnormalities (CA) are an important cause of RPL because the gametes of carriers may have chromosomal imbalance which is lethal to the fetus. Therefore, the identification of CA helps to provide information about likely outcome of pregnancy in carriers. The objective of this study was to determine the frequency and types of CA in RPL. MethodsThe study group consisted of individuals with RPL seen at a tertiary care center in South India from 2001 to 2019, whose karyotypes were reviewed retrospectively. Cytogenetic analysis was performed on peripheral blood using standard protocols. The number of metaphases analyzed per patient was 20 and extended up to 50 for confirmation of low-level mosaicism. ResultsThere were 3488 individuals (1663 couples and 162 where only partner was tested of whom 104 were females). The frequency of CA was 3.6% (127/3488) (M:F ratio of 1:2.6). Structural aberrations were seen in 2.5% (90/3488) and numerical aberrations of sex chromosomes in 1.1% (37/3488) of patients. Structural aberrations included 68 balanced translocations including one three-way translocation, seven inversions, one insertion and duplication each, and 14 Robertsonian translocations. There was one patient each with Turner syndrome (TS) and 47,XYY syndrome. We had 37 mosaics, comprising 29 with mosaic TS and 6 with triple X mosaicism and 2 with mosaicism for balanced translocation. ConclusionThe frequency of CA is comparable to the literature. We have described a few less commonly seen aberrations as well as sex chromosomal aneuploidies, almost all of which were due to low-level mosaicism.

B-Cell Acute Lymphoblastic Leukemia with iAMP21 in a Patient with Constitutional Ring Chromosome 21

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is associated with various specific cytogenetic and molecular markers that significantly influence treatment and prognosis. Intrachromosomal amplification of chromosome 21 (iAMP21) defines a rare distinct cytogenetic subgroup of childhood B-ALL, which is characterized by amplification of region 21q22.12 comprising the RUNX1 gene. Constitutional structural chromosomal abnormalities involving chromosome 21 confer an increased risk for B-ALL with iAMP21. Here, we report the development of B-ALL with iAMP21 in a 9-year-old child with a constitutional ring chromosome 21, r(21)c, uncovered after B-ALL diagnosis. Cytogenetic and microarray analysis of the post-therapy sample revealed an abnormal chromosome 21 lacking a satellite and having a deletion of the terminal 22q22.3 region, consistent with a constitutional ring chromosome 21, r(21)(p11.2q22). On a retrospective analysis, this ring chromosome was observed in the normal cells in the pre-treatment diagnostic specimen. Constitutional ring chromosome 21 may remain undetected in patients with mild or no neurodevelopmental phenotype, posing an unknown lifelong risk of developing B-ALL with iAMP21. Individuals with constitutional structural chromosome 21 rearrangements such as ring 21 require a close surveillance and long-term follow-up studies to establish their risk of B-ALL relapse and possibility of developing other malignancies. Germline analysis is recommended to all pediatric patients with iAMP21-related B-ALL to rule out structural chromosome 21 rearrangements and to elucidate molecular mechanisms of iAMP21 formation.

Constitutional pericentric inversion of chromosome 16, inv(16)(p13.1q22), mimicking acute myeloid leukemia.

An acquired abnormality, inv(16)(p13q22), is a hallmark of acute myeloid leukemia with eosinophilia (AML M4Eo), which leads to leukemogenesis by forming the CBFB::MYH11 fusion gene [1]. We experienced a case of inv(16)(p13.1q22) discovered incidentally during bone marrow examination without evidence of AML. A 64-year-old woman was referred to our hospital because of hypergammaglobulinemia. She was being treated for rheumatoid arthritis, but had no past and family history of AML. Laboratory examination showed polyclonal gammopathy but no significant abnormalities in complete blood count with differential. Bone marrow picture showed a normocellular marrow and mild increase in plasma cells to 3.8% (reference range, 0.2%–1.7%), but no evidence of hematological malignancy. Surprisingly, chromosome analysis of the bone marrow cells revealed that all 20 cells had inv(16)(p13.1q22) mimicking AML M4Eo (Figure 1A). We therefore performed fluorescence in situ hybridization (FISH) analysis of the bone marrow cells by using the Vysis CBFB Dual Color Break Apart Rearrangement Probe (Abbott Molecular Diagnostics, Des Plaines, IL, USA). The splitting of the red and green signals reflecting truncation of the CBFB locus on chromosome 16q22 was not observed (Figure 1B). In addition, a multiplex reverse transcriptase-polymerase chain reaction assay covering 28 leukemia-specific fusion transcripts including CBFB::MYH11 was performed by using the HemaVision-28Q kit (VERITAS, Tokyo, Japan), but none of them was detected. Therefore, it was suggested that the chromosome inversion of this patient did not disrupt the CBFB gene. High-resolution chromosome analysis of the phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes also revealed inv(16)(p13.1q22) in all 20 cells, indicating a constitutional abnormality of chromosome 16 (Figure 1C). Thus, this patient was not misdiagnosed as AML M4Eo and has been followed up without treatment. To the best of our knowledge, only a few cases with inv(16)(p13q22) unrelated to AML have been reported [2-5]. All of these were concluded to be constitutional abnormalities, and some cases have been confirmed as familial onset. In these reports, there was no misdiagnosis of AML M4Eo in individuals without hematological malignancy, and in the case of chronic myeloid leukemia with t(9;22)(q34;q11) and inv(16)(p13q22), FISH analysis showed no abnormality of the MYH11 gene and inv(16)(p13q22) was also found in her healthy father, which avoided misdiagnosis as an additional cytogenetic abnormality in chronic phase [4]. Therefore, although extremely rare, we should be aware of the presence of constitutional chromosome abnormalities mimicking hematological malignancies, and it is important to perform further tests such as FISH and genomic analysis for differential diagnosis. We thank Yoshiko Sato, MT (LSI Medience Corporation, Tokyo, Japan), for her technical support. The authors declare that there is no conflict of interest. All procedures in this study were performed in accordance with the principles of the Declaration of Helsinki and the institutional guidelines. Informed consent was obtained from the patient and her family. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Recurring germline mosaicism in a family due to reversion of an inherited derivative chromosome 8 from an 8;21 translocation with interstitial telomeric sequences

BackgroundMosaicism for chromosomal structural abnormalities, other than marker or ring chromosomes, is rarely inherited.MethodsWe performed cytogenetics studies and breakpoint analyses on a family with transmission of mosaicism for a derivative...

B‐cell acute lymphoblastic leukemia with iAMP21 in a patient with Down syndrome due to a constitutional isodicentric chromosome 21

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is associated with various specific cytogenetic and molecular markers that have significant influence on treatment and prognosis. A subset of children has a much higher risk of developing B-ALL due to constitutional genetic alterations such as trisomy 21 (Down's syndrome). In these patients, B-ALL is often associated with specific genomic profiles leading to leukemic transformation. In rare cases, constitutional structural chromosomal abnormalities involving chromosome 21, such as the der(15;21) Robertsonian translocation and a ring 21 chromosome, have been associated with intrachromosomal amplification of chromosome 21 (iAMP21) B-ALL. Here, we report the development of B-ALL in a child with Down's syndrome who carries a constitutional isodicentric chromosome 21 [idic(21)], described previously by Putra et al., 2017. This idic(21) appeared to be unstable during mitosis, leading to somatic rearrangements consistent with iAMP21 amplification, resulting in the development of leukemia. In this case, a single constitutional structural chromosome 21 rearrangement resulted in a B-ALL with Down syndrome-associated genomic lesions as well as genomic lesions not common to the Down syndrome subtype of B-ALL. Our findings highlight the need for counseling of individuals with constitutional structural chromosome 21 rearrangements regarding their risks of developing a B-ALL.

NEUROBLASTOMA IN A CASE OF CONGENITAL ADRENAL HYPERPLASIA

The majority of neuroblastomas are sporadic and not correlated with any specific constitutional germline chromosomal abnormality, inherited predisposition, or associated congenital anomalies. We report here a 1.5-year-old girl with a diagnosis of 21 hydroxylase deficiency and neuroblastoma. Neuroblastoma in a known case of congenital adrenal hyperplasia has rarely been reported. Based on our literature review, this is the fifth case report of congenital adrenal hyperplasia and neuroblastoma.

Genetic predisposition in pediatric oncology.

Identifying patients with a genetic predisposition for developing malignant tumors has a significant impact on both the patient and family. Recognition of genetic predisposition, before diagnosing a malignant pathology, may lead to early diagnosis of a neoplasia. Recognition of a genetic predisposition syndrome after the diagnosis of neoplasia can result in a change of treatment plan, a specific follow-up of adverse treatment effects and, of course, a long-term follow-up focusing on the early detection of a second neoplasia.Responsible for genetic syndromes that predispose individuals to malignant pathology are germline mutations. These mutations are present in all cells of conception, they can be inherited or can occur de novo.Several mechanisms of inheritance are described: Mendelian autosomal dominant, Mendelian autosomal recessive, X-linked patterns, constitutional chromosomal abnormality and non-Mendelian inheritance.In the following review we will present the most important genetic syndromes in pediatric oncology.

Characterization of renal cell carcinoma‐associated constitutional chromosome abnormalities by genome sequencing

Constitutional translocations, typically involving chromosome 3, have been recognized as a rare cause of inherited predisposition to renal cell carcinoma (RCC) for four decades. However, knowledge of the molecular basis of this association is limited. We have characterized the breakpoints by genome sequencing (GS) of constitutional chromosome abnormalities in five individuals who presented with RCC. In one individual with constitutional t(10;17)(q11.21;p11.2), the translocation breakpoint disrupted two genes: the known renal tumor suppressor gene (TSG) FLCN (and clinical features of Birt‐Hogg‐Dubé syndrome were detected) and RASGEF1A. In four cases, the rearrangement breakpoints did not disrupt known inherited RCC genes. In the second case without chromosome 3 involvement, the translocation breakpoint in an individual with a constitutional t(2;17)(q21.1;q11.2) mapped 12 Kb upstream of NLK. Interestingly, NLK has been reported to interact indirectly with FBXW7 and a previously reported RCC‐associated translocation breakpoint disrupted FBXW7. In two cases of constitutional chromosome 3 translocations, no candidate TSGs were identified in the vicinity of the breakpoints. However, in an individual with a constitutional chromosome 3 inversion, the 3p breakpoint disrupted the FHIT TSG (which has been reported previously to be disrupted in two apparently unrelated families with an RCC‐associated t(3;8)(p14.2;q24.1). These findings (a) expand the range of constitutional chromosome rearrangements that may be associated with predisposition to RCC, (b) confirm that chromosome rearrangements not involving chromosome 3 can predispose to RCC, (c) suggest that a variety of molecular mechanisms are involved the pathogenesis of translocation‐associated RCC, and (d) demonstrate the utility of GS for investigating such cases.

Практические рекомендации по обеспечению качества и надежности цитогенетических исследований

Практические рекомендации (ПР) по обеспечению качества и надежности пренатальных и постнатальных цитогенетических исследований подготовлены рабочей группой Российского общества медицинских генетиков. Их основой послужили Европейские стандарты для цитогенетических и молекулярно-цитогенетических исследований конститутивных и приобретенных хромосомных аномалий, подготовленные постоянной рабочей группой «Цитогенетики и общество» Европейской цитогенетической ассоциации (Е.С.А.). ПР посвящены цитогенетической диагностике конститутивных нарушений, направлены на стандартизацию лабораторно-генетической службы и призваны способствовать совершенствованию цитогенетической службы РФ. В ПР рассматривают вопросы контроля качества и надежности цитогенетических и молекулярно-цитогенетических методов, используемых в цитогенетических лабораториях в настоящее время. The Working group of Russian Society of Medical Geneticists prepared these Recommendations based on General Guidelines and Quality Assurance for Cytogenetics: a common European framework for quality assessment for constitutional,acquired and molecular cytogenetic investigations (European Cytogeneticists Association (E.C.A.) Permanent Working Group for Cytogenetics and Society). This document is devoted to prenatal and postnatal (molecular) cytogenetic diagnosis of the constitutional chromosomal abnormalities, is aimed to define quality framework and to improve the activity of cytogenetic laboratories in Russian Federation. The Recommendations include aspects of quality control and safety for most of the methods currently employed by cytogenetic laboratories.

Decrease of spermatozoa with an unbalanced chromosome content after cell sorting in men carrying a structural chromosomal abnormality.

We showed that in men with a constitutional chromosomal abnormality, DNA fragmentation was significantly higher in chromosomally unbalanced spermatozoa than in spermatozoa with a normal or balanced chromosomal content. These results could be explained by a phenomenon already described in infertile men: abortive apoptosis. To determine whether magnetic-activated cell separation could select spermatozoa with lower levels of DNA fragmentation and unbalanced chromosome content in men carrying a structural chromosomal abnormality. The spermatozoa of ten males with a chromosomal rearrangement were separated into two populations using magnetic-activated cell separation (annexin V (-) and annexin V (+) fractions), in order to study meiotic segregation by fluorescence insitu hybridization, the percentage of spermatozoa with an externalization of phosphatidylserine by annexin V staining and DNA fragmentation by TdT-mediated dUTP nick-end labeling on the whole ejaculate and on selected spermatozoa in the same patient. For all patients, the percentage of spermatozoa with externalization of phosphatidylserine decreased in the annexin V (-) fraction and increased in the annexin V (+) fraction as compared to the frozen-thawed semen sample. The rates of DNA fragmentation were statistically much lower in the annexin V (-) fraction when compared to the rate before magnetic-activated cell separation for all but one patient. Conversely, we observed a statistically significantly higher rate of DNA fragmentation in the annexin V (+) fraction for six patients. After magnetic-activated cell separation, there was a significant increase of normal/balanced spermatozoa in the fraction of annexin V (-) for all patients. Conversely, we observed a significant decrease in the fraction of annexin V (+) for seven patients. Magnetic-activated cell separation is a promising tool for increasing the selection of healthy spermatozoa, with a decrease in the number of spermatozoa with externalization of phosphatidylserine, DNA fragmentation, and chromosome unbalance, for use in assisted reproductive technologies such as intracytoplasmic sperm injection for males with a chromosomal structural abnormality.

Correlation between prognostic chromosomal segregation and detected rearrangements in preimplantation embryos in a balanced translocation carrier

Introduction Individuals with balanced translocations are estimated to be around 1 % of the patients with infertility. A reciprocal translocation usually involves breakage of two non-homologous chromosomes with exchange of fragment with different size. The medical history of affected couples includes abortions, stillbirth, congenital anomalies, possible mental retardation and unsuccessful IVF attempts. It is hard to define the exact risk of unbalanced karyotypes in gametes, but it is accepted that it could be more than 80%. Preimplantation genetic screening (PGS) is strongly recommended in cases with chromosome rearrangements allowing the study of female gamete segregation. Material and Methods In the present case we performed two IVF-PGS cycles in a couple with a 34 years old woman with karyotype 46 XX, t(1;16)(q12;q13). Altogether, 14 embryos on day 3 where biopsied and tested using the 24sure (Illumina Inc., USA) protocol for BAC arrays. Results Out of the 14 tested embryos only two were euploid, five embryos had unbalanced genome due to the involvement of the chromosomes with the parental translocation. The other embryos had ‘sporadic'aneuploidy. After the PGS an embryotransfer of two euploid embryos was performed with one healthy baby born. Discussion Commonly more than 60 % of embryos obtained from patients with reciprocal translocations carry abnormal chromosomal constitution and about 1:28/30 are normal. In this case the percentage of unbalanced embryos - 5/14 (∼ 36 %) was significantly lower than the expected according to the published data. However, other independent aneuploidies also co-exist, most of which are age dependent. Conclusions The theoretical percentage of embryos with unbalanced karyotypes and the data from the clinical practice after performing PGS in IVF patients with balanced translocations does not match in every case. The phenomenon reveals the need of additional studies about the molecular mechanisms of chromosomal segregation in human gametes and preimplantation embryos delivered from balanced translocation carriers.

Prenatal diagnosis in Italy.

In Italy, there are about 560,000 births per year. The number of prenatal diagnoses (PND) performed is estimated at 80,000 examinations per year, but no official data are available regarding the distribution of the different procedures. There are no official registers, either at a national or at a regional level, concerning PND and particularly the invasive procedures (as amniocentesis, chorionic villus sampling, chordocentesis). Thanks to the direct interest of some scientific societies, such as the Italian Association of Medical Cytogenetics, the Italian Association of Medical Genetics, the Italian Society for the Study of Metabolic Hereditary Diseases and the Italian Society of Gynaecology and Obstetrics, it has been possible to identify the number and distribution of public and private structures interested in genetic counselling and prenatal diagnosis during the last decades. As to the congenital malformations, there is a regional epidemiological system of surveys (started in 1982) co-ordinated by the Epidemiological and Biostatistical Laboratory of the 'Istituto Superiore di Sanità' (National Board of Health). This institution has published data for the period between 1986 and 1990 concerning the trend of incidence for the most important malformations at birth. Cytogenetic PND in public services is allowed for the following indications: maternal age 35 and over, previous child with a chromosomal anomaly, parent with a constitutional chromosomal abnormality and abnormal findings at the ultrasound examinations. Current methods in use consist in echography, amniocentesis, chorionic villus sampling, fetal blood sampling and maternal serum screening. At the moment, new approaches to the fetal tissue sampling are, as follows: amniotic fluid filtration, transcervical cell sampling and isolation of fetal cells from maternal blood. Furthermore, areas under development are 3D sonography and first-trimester anatomic survey sonography. PND is financed by regional laws, the National Health Service and private funds. There is a current legislation on termination of pregnancy (Law 194/1978). This law permits voluntary interruption of pregnancy within the first 90 days, while it is permitted between 90 and 180 days only in cases of severe fetal anomalies and over 180 days for serious risks for the woman's life: but it is necessary to do everything to save the fetal life. No law has been issued yet on pre-implantation diagnosis. Presently, the major problems are: the unbalanced distribution of financial resources among the different regions, the irrational number and distribution of centres for PND, inadequate prenatal counselling, especially in central/southern Italy, where counselling is somehow lacking. Therefore, guidelines for appropriate prenatal counselling should be established. For the future, we believe that the best results in this field are probably related to the advances of research (there is a target programme of the Italian National Research Council called 'Genetic Engineering', which is in its fourth year of financing). This programme will hopefully be cost-effective and improve the quality of PND so that more congenital anomalies can be detected at lower expenses in the future.

Síndrome de Down mosaico y leucemia linfoblástica aguda de células B: reporte de un caso

Down syndrome (DS) or trisomy 21 is a constitutional chromosomal abnormality, which may be mosaic in 1 % to 4 % of cases. DS mosaic diagnosis is difficult because most patients have a normal phenotype and show no significant clinical abnormalities. Patients with DS have a higher risk of developing acute leukemia such as acute lymphoblastic leukemia (ALL). We report the case of a 19-year old woman with mosaic trisomy 21 and ALL.

A marker chromosome in post-transplant bone marrow.

Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice.

Preferential Y-Y pairing and synapsis and abnormal meiotic recombination in a 47,XYY man with non obstructive azoospermia.

Back groundMen with 47, XYY syndrome are presented with varying physical attributes and degrees of infertility. Little information has been documented regarding the meiotic progression in patients with extra Y chromosome along with the synapses and recombination between the two Y chromosomes.MethodsSpermatocyte spreading and immunostaining were applied to study the behavior of the extra Y chromosome during meiosis I in an azoospermia patient with 47, XYY syndrome and results were compared with five healthy controls with proven fertility.ResultsThe extra Y chromosome was present in all the studied spermatocytes of the patient and preferentially paired and synapsed with the other Y chromosome. Consistently, gamma-H2AX staining completely disappeared from the synapsed regions of Y chromosomes. More interestingly, besides recombination on short arms, recombination on the long arms of Y chromosomes was also observed. No pairing and synapsis defects between homologous autosomes were detected, while significantly reduced recombination frequencies on autosomes were observed in the patient. The meiotic prophase I progression was disturbed with significantly increased proportion of leptotene, zygotene cells and decreased pachytene spermatocytes in the patient when compared with the controls.ConclusionsThese findings highlight the importance of studies on meiotic behaviors in patients with an abnormal chromosomal constitution and provide an important framework for future studies, which may elucidate the impairment caused by extra Y chromosome in mammalian meiosis and fertility.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-016-0218-z) contains supplementary material, which is available to authorized users.

Inadvertent Transmission of a Donor’s Constitutional Chromosome Abnormality after Hematopoietic Stem Cell Transplantation

A pre-transplant screening work-up of donors for allogeneic hematopoietic stem cell transplantation (HSCT) is essential. Inadvertent transmission of malignancy from donors with subclinical diseases to recipients has been reported recently in several cases. A 49-year-old male was diagnosed with acute myeloid leukemia. He underwent a course of induction chemotherapy and achieved cytogenetic complete remission (CR). He was treated with an additional cycle of consolidation chemotherapy followed by full matched sibling allogeneic HSCT due to an additional deletion in 9q known as an adverse prognostic factor. Post transplantation bone marrow biopsy revealed molecular CR, but conventional cytogenetics identified the presence of 46,XY,t(1:2)(p32:q35). A cytogenetic analysis of the donor graft specimen revealed t(1:2). We confirmed the donor origin of t(1:2). We report the first case of a person with constitutional t(1;2) serving as a stem cell donor.

A Case Report of Solitary Fibrous Tumor in the Axilla of a 4-year-old Girl with Additional Marker Chromosome

Solitary fibrous tumor (SFT) is uncommon and known to affect in middle-aged adults, with rare reports of occurrences in children. Although frequently involving the pleura, recent reports show that SFT may also involve extrapleural sites. SFT is known as a benign tumor, but in some cases SFT recurs, invades locally, or shows malignant transformation. We experienced a case of SFT that developed in the axilla of a 4-year-old girl with multiple congenital anomalies with constitutional chromosomal abnormality of 46,XX[44]/47,XX,+mar[11]. Her tumor could not be surgically resected due to the patient’s multiple anomalies including congenital heart disease, chronic lung problem and seizure disorder. She died of congestive heart failure with respiratory failure due to tumor growth. This report is meaningful not only because SFT affected a pediatric patient with a constitutional chromosomal abnormality, but also because the tumor originated from the axillary area, a site of origin rarely reported for SFTs. pISSN 2233-5250 / eISSN 2233-4580 http://dx.doi.org/10.15264/cpho.2015.22.2.171 Clin Pediatr Hematol Oncol 2015;22:171∼175

Y chromosome microdeletions and alterations of spermatogenesis, patient approach and genetic counseling

Infertility affects 15% of couples at reproductive age and human male infertility appears frequently idiopathic. The main genetic causes of spermatogenesis defect responsible for non-obstructive azoospermia and severe oligozoospermia are constitutional chromosomal abnormalities and microdeletions in the azoospermia factor region of the Y chromosome. The improvement of the Yq microdeletion screening method gave new insights in the mechanism responsible for the genesis of Yq microdeletions and for the consequences of the management of male infertility and genetic counselling in case of assisted reproductive technology.