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. 2022 Feb 7;13(3):254–260. doi: 10.1159/000519965

A New Case of Rare Microdeletion 10q22.3q23 along with Mosaic Klinefelter Syndrome Associated with Facial Dysmorphic Finding, Atrial Ventricular Septal Defect, and Motor Retardation

Firdevs Dincsoy Bir a, Fatma Silan b,*, Jelena Velickovic c, Mehmet Berkay Akcan b, Ozturk Ozdemir b
PMCID: PMC9149477  PMID: 35707596

Abstract

The chromosome 10q22.3q23.2 deletion syndrome is characterized by craniofacial dysmorphic features, developmental delay, congenital heart defect, and hand/foot abnormalities. In this study, we report a patient carrying a microdeletion of 7.5 Mb at 10q22.3q23.2 and in addition a mosaicism mos 47,XXY[47]/46,XY[23]. This male patient was 3 years and 3 months years old at the time of genetic evaluation. Atrial ventricular septal defect (AVSD), mild hypotonia, torticollis, and left-sided club foot were noticed after birth. The boy had surgical correction of the AVSD and the club foot. His dysmorphic features were frontal bossing, overfolded ear helix, hypertelorism, epicanthal folds, broad base of nose, flat nasal bridge, full cheeks, thick lips, micrognathia, and joint hyperextensibility. His speech/language development was delayed. Klinefelter syndrome is one of the most common congenital chromosomal abnormalities, but usually it is detected in puberty or in adulthood when reproductive failure occurs. Deletions in the 10q22.3q23.2 region are rare, and previously only a few numbers of cases were described with this microdeletion, but none of them together with Klinefelter syndrome and it could be associated with our case clinical features. The new case described will improve understanding the phenotype associated with 10q22.3q23.2 microdeletions. By presenting this case, we aimed to improve the understanding of the phenotype caused by the rare 10q22.3q23.2 deletion and to show the rare coexistence of this deletion with Klinefelter syndrome.

Keywords: 10q22.3q23.2 microdeletion, Atrial ventricular septal defect, Klinefelter syndrome, Language delay, Mosaicism

Established Facts

  • Reported 10q22.3q23.2 microdeletions are associated with the recently described and rare deletion syndrome.

  • To the best of our knowledge, to date 15 microdeletions at this locus have been reported in the literature along with different chromosomal anomalies.

Novel Insights

  • We report a new case of a boy with microdeletion at 10q22.3q23.2 with atrial ventricular septal defect and motor retardation.

  • This is the first case of a microdeletion 10q22.3q23.2 together with mosaic Klinefelter syndrome and could be related with the patient's phenotype.

Introduction

When chromosomal banding techniques became available in the 1970s, the cytogenetic basis of many syndromes was revealed. The development of subtelomeric fluorescence in situ hybridization (FISH), targeting all telomeres in a single assay, led to a shift from the original “phenotype-first” approach to a “genotype-first” approach. In the absence of a recognizable phenotype, individuals were screened by FISH for novel submicroscopic chromosomal abnormalities. Using new molecular karyotyping techniques, such as subtelomeric MLPA and microarray analysis, reverse phenotyping has proven to be successful by the constantly increasing list of microdeletion/microduplication syndromes. Great advances in molecular cytogenetic analyzes have led to a significantly higher number of detections of microdeletion/microduplication syndromes [Slavotinek et al., 2008; van Bon et al., 2011; Nevado et al., 2014]. Chromosome 10q22.3q23.2 deletion syndrome is characterized by craniofacial dysmorphic features, developmental delay, palate alterations, congenital heart defect, and hand/foot abnormalities, and less common clinical features are hypotonia, autism, and joint hyperextensibility [Coelho Molc et al., 2017]. The 10q22.3q23.2 region is flanked by a complex set of low-copy repeats (LCRs), designated LCR3 and LCR4, and the presence of LCRs in this region suggests that this locus has an increased susceptibility to chromosomal rearrangements [Balciuniene et al., 2017]. Only 15 deletions with breakpoints within LCRs 3/4 have been described, and additional chromosome abnormalities (2q36.3 duplication, 47,XYY, 16q12.1 deletion) were observed in 3 of the 15 patients [Coelho Molc et al., 2017]. Our patient is the fourth patient with 10q22q23 deletion syndrome and an additional chromosome abnormality.

Klinefelter syndrome (KS) is one of the most common congenital chromosomal abnormalities (diagnosed as additional X chromosomes) and one of the most common causes of infertility. About 80% of KS patients show a 47,XXY karyotype, 20% have other numeric sex chromosome abnormalities, mosaicism, or structurally abnormal sex chromosomes [Lanfranco et al., 2004; Frühmesser and Kotzot, 2011]. Apart from that, various other karyotypes have been described, including 46,XX in males, 47,XXY in females, 47,XX,der(Y), or other sex chromosome abnormalities (48,XXX, 48,XXYY, and 49,XXXXY) [Frühmesser and Kotzot, 2011]. Although the clinical finding is variable, mosaic forms have a milder phenotype than non-mosaics. Boys with 47,XXY may have hypospadias, small phallus, cryptorchidism, developmental delay, especially with expressive language skills [Caldwell et al., 1972; Walzer et al., 1978; Graham et al., 1988]. The typical symptoms usually include tall stature, narrow shoulders, broad hips, gynecomastia, small testes, absent spermatogenesis, etc [Frühmesser and Kotzot, 2011]. Numerous studies have shown that early detection of this condition is very important in order to reduce the clinical features with proper neurodevelopmental treatment [Samango-Sprouse et al., 2019]. This could be very helpful in order to reduce the risk for later language and literacy challenges and optimize academic, social, and behavioral difficulties later in life [John et al., 2019].

In this study, we report a patient carrying a microdeletion of 7.5 Mb at 10q22.3q23.2 together with mosaicism mos 47,XXY[47]/46,XY[23] [ISCN, 2016]. The main aim of this report is to present the new case with microdeletion at 10q22.3q23.2 which probably causes the clinical feature in our patient. Additionally, to the best of our knowledge, this is the first case with above-mentioned microdeletion along with mosaic KS. Therefore, with this case report, we wanted to contribute to a better understanding of the combined effect of multiple chromosomal rearrangements.

Case Report

A 3 years and 3 months old boy was referred for medical genetic consultation to the Department of Medical Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey because of multiple anomalies. The proband is the first child born to non-consanguineous parents. His family history was unremarkable. The patient was born at term and his birth weight was 3,100 g. Atrial ventricular septal defect (AVSD), mild hypotonia, torticollis, and left-sided club foot were noticed after birth. The boy had surgical correction of the AVSD and the club foot. His dysmorphic features were frontal bossing, overfolded ear helix, hypertelorism, epicanthal folds, broad base of nose, flat nasal bridge, full cheeks, thick lips, micrognathia, and joint hyperextensibility. He had normal external genital development for the present age. Weight, height, and head circumference were normal. His speech/language development was delayed but motor development was normal. Especially his expressive (speaking) language skills were backward than receptive (understanding) skills. Another clinical feature observed in our patient was hypothyroidism. Maternal age at birth was 33 years and the father was 34 years old. The father has a delayed speech history and the mother and mother's family are suffering from hypothyroidism.

Methods and Results

Cytogenetic and Molecular Cytogenetic Findings

Heparinized and blood-EDTA samples were used for lymphocyte culture and total genomic DNA isolation (Pure Link, Genomic DNA isolation kit, Invitrogen, Thermo Fisher Scientific) for the present case and his parents. Metaphase spreads were evaluated after trypsin-GTG banding technique. All chromosomes were also identified by Agilent SurePrint G3 Human CGH 60K MicroArray Platform (Agilent Technologies) for the advanced detection of affected gene(s) in the chromosomal break points for the presented case. The patient was diagnosed by comparing different techniques of conventional cytogenetic karyotype analysis, microarray-CGH (Agilent 60K platform), and FISH methods. Cytocell FISH probes for chromosomes X and Y (centromeric region p11.1q11.1), developed and produced in the UK, were used for FISH analysis.

Cytogenetic Analysis

Cytogenetic analysis was performed with trypsin GTG banding technique for the patient's and his parent's lymphocytes. The patient's karyotype showed a mos 47,XXY[47]/46,XY[23]. The parents' karyotypes were normal.

Molecular cytogenetic findings were a 7,547-kb heterozygous deletion on chromosome 10q22.3q23.2 (81,641,91–89,189,067; hg 19) and a duplication of the X chromosome (Fig. 1). After conventional G-banding karyotype analysis, the additional X chromosome was identified by FISH (Fig. 2). Metaphase spreads were analyzed by Y and X chromosome specific centromeric FISH probes. Metaphase and interphase cells revealed a centromeric region profile after FISH analysis. Nine metaphases (mos 47,XXY[8]/46,XY[1]) and 46 interphases (mos 47,XXY[26]/46,XY[20]) were scored by FISH analysis, and 15 metaphases (mos 47,XXY[13]/46,XY[2]) were scored by karyotype analysis. Unfortunately, we did not analyze different germ layers (epithelial cells from the buccal smear) to confirm the level of mosaicism.

Fig. 1.

Fig. 1

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47,XXY karyotype of the patient.

Fig. 2.

Fig. 2

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FISH analysis with centromeric probes for X and Y chromosomes (centromeric region p11.1q11.1) shows the XXY profile of metaphase (a) and interphase (b) cell nuclei. Thin arrows indicate the X chromosomes and the bold arrow shows the signal for the Y chromosome.

Array Analysis

Whole genomic DNA was used as a template for microarray-CGH analysis with 60-mer oligonucleotide CGH arrays (Agilent Technologies). Total genomic DNA was digested using AluI and RsaI enzymes (Agilent Technologies), labeled with cyanine 3-dUTP (Cy3-dUTP) and cyanine 5-dUTP (Cy5-dUTP), respectively, by using Klenow DNA enzyme following the manufacturer's instruction. Target DNAs from the patient, reference, and human Cot-1 DNAs were dissolved, denatured, and hybridized to the CGH array at 65°C for 24 h. After hybridisation with oligoprobes the 60K glass slides were washed, scanned, and the microarray images were analyzed using Agilent C microarray scanner (model/tip Agilent Technologies) and the data were imported into Default Analysis Method-CGH v2 (Agilent Technologies) for evaluation. For analysis we used Agilent SurePrint G3 Human CGH 60K microarray platform and AgilentCytogenomics 4.0.2.21 software. When we performed array-CGH analysis of all chromosomes for the presented case we detected the 10q22.3q23.2 deletion and also a duplication of the X chromosome (Fig. 3a), (arr[hg19] 10q22.3q23.2(81,641,918-89,189,067)×1 arr[hg19]X×2). Figure 3b shows chromosome 10 with a 7,547-kb microdeletion detected on 10q22.3q23.2, while Figure 3c illustrates the duplicated probe profiles for the X chromosome. Unfortunately, the microdeletion detected in the array analysis was not verified by any other method. Except for the deletion detected in the 10q22.3q23.2 region, no additional pathological CNV was identified in the patient. Chromosomal microarray analysis of the parents showed normal karyotypes.

Fig. 3.

Fig. 3

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Array-CGH profiles of all chromosomes for the presented proband. a Genome view of the proband with the 10q22.3q23.2 deletion (yellow arrow) and the duplication of the X chromosome (blue arrow). b Chromosome 10 indicating a 7.5-Mb microdeletion at 10q22.3q23.2 (blue arrow) between 81.641 and 89.189 basepairs; hg 19 is shown by dotted lines. c Duplicated probe profiles for the X chromosome.

Discussion and Conclusion

Boys and men with KS have an extra copy of multiple genes on the X chromosome. The activity of these genes may disrupt many aspects of development, including sexual development before birth and at puberty, and are responsible for the common signs and symptoms of KS. Less than 10% of individuals with KS have the mosaic form, the extra X chromosome being only present in some of their cells. Individuals with mosaic KS may have milder signs and symptoms than those with the extra X chromosome in all of their cells, depending on what proportion of cells have the additional chromosomes. In our case, 47 out of 70 cells were detected with an additional X chromosome.

Only 15 microdeletions at 10q22.3q23.2 have been reported in the literature, and additional chromosome abnormalities (2q36.3 duplication, 47,XYY, 16q12.1 deletion) were observed in 3 of 15 patients [Coelho Molc et al., 2017]. Our patient is the fourth patient with 10q22q23 deletion syndrome and an additional chromosome abnormality (47,XXY).

Patients with different submicroscopic aberrations have been recognized by a specific combination of clinical symptoms. Deletions of 10q22.3q23.2 have been characterized by cognitive and behavioral abnormalities. This region is characterized by a complex set of low-copy repeats (LCRs), which can give rise to various genomic changes that could be associated with various clinical features. Most individuals with the LCR3-4 deletions have developmental delay, mainly affecting speech but also learning difficulties and language delay. In addition, macrocephaly, mild facial dysmorphisms, cerebellar anomalies, cardiac defects, and congenital breast aplasia were observed in some patients. Cardiac evaluation was not uniform in all patients with specific microdeletions, but in some of the previously reported cases PDA (persisted ductus arteriosus) or AVSD was shown. In addition, some of the reported cases had additional chromosome abnormalities, such as duplication 2p36.3, 47,XYY karyotype, and in our case mosaic KS, which could influence their phenotype. Similar phenotypic variability could be explained by these additional rearrangements. However, some of these differences could be due to the disruption of topologically associated domains (TAD).

A TAD is a self-interacting genomic region, meaning that DNA sequences within a TAD physically interact with each other more frequently than with sequences outside a TAD region. The functions of TADs are not fully understood and are still a matter of debate. Most of the studies indicate that TADs regulate gene expression by limiting the enhancer-promoter interaction to each TAD. Since deletions and duplications can alter the relationship between genes and their regulatory elements, the disruption of TADs could explain why different size deletions in the same region of the genome may result in patients showing apparent variability in clinical features without having different significant differences in the affected gene content. The disruption of these structures by genomic rearrangements can result in gene misexpression and disease [Lupianez et al., 2016; Muro et al., 2019].

There are 16 OMIM genes within the 7.5 Mb-deleted region at 10q22.3q23.2 detected in our patient. Some of these genes are MAT1A, CDHR1, RGR, LDB3, BMPR1A, and GLUD1. Deletions of this chromosome region including the BMPR1A gene have been associated with dysmorphic facies, developmental delay, and multiple congenital anomalies [van Bon et al., 2011]. Heterozygous point mutations or partial deletions of the BMPR1A gene are associated with the juvenile polyposis syndrome, infantile form (OMIM 174900) [Howe et al., 2001]. But among patients with 10q22.3q23.2 deletions, only those having both BMPR1A and PTEN genes deleted have been observed with juvenile polyposis syndrome [Menko et al., 2008]. PTEN is not present in the patients with a 10q22.3q23.2 deletion who were reported to have juvenile polyposis of infancy or to have developed the polyposis phenotype [Petrova et al., 2014]. The deletion in the presented patient did not contain the PTEN gene and he had no gastrointestinal complaints.

Seven of the 16 reported 10q22.3q23.2 deletion patients (including also our patient) have congenital heart disease. For cardiac defects, BMPR1A and GRID1 were proposed as candidate genes because of their association with cardiac structures and function. BMPR1A has been shown to be deleted in individuals who have been reported with overlapping deletions and cardiac septal defects. Cardiac specific deletion of BMPR1A disrupts morphogenesis in mice, showing ventricular septum, trabeculae, compact myocardium, and endocardial cushion defects [von Bon et al., 2011]. We assume that this gene is also responsible for AVSD in our case. Gaussin et al. [2002] reported that cardiac-specific deletion of BMPR1A (alk3) disrupts cardiac morphogenesis in mice, resulting in ventricular septum, trabeculation, and endocardial cushion defects. Breckpot et al. [2012] suggested that sequencing and copy number analysis of BMPR1A should be considered in patients with (atrioventricular) septal defects, especially when associated with facial dysmorphism and anomalous growth, because BMPR1A may have a crucial role in the genesis of congenital heart defects in patients with interstitial 10q deletions. D'Alessandro et al. [2016] performed whole-exome sequencing in 81 unrelated probands with atrioventricular septal defect to identify potential causal variants in a comprehensive set of 112 genes. Three rare missense variants in BMPR1A were reported in 3.7% of AVSD cases, compared with 0.7% of controls from the Exome Variant Server (EVS) (OR 5.3; p = 0.02). All 3 nonsynonymous variants in the BMPR1A gene were exceptionally rare and predicted to be damaging [D'Alessandro et al., 2016]. The presented case had AVSD which may be partly caused by the deletion in the BMPR1A gene. In the literature KS was reported with some syndromes like Down syndrome, Prader-Willi syndrome, and Incontinentia pigmenti, an X-linked dominant disorder [Rego et al., 1997; Rodriquez et al., 2017; Williams et al., 2017]. To the best of our knowledge, the 10q22.3q23.2 deletion syndrome and KS together have not been previously reported in the literature. The presented case had decreased speech ability that can be a symptom of KS or 10q22.3q23.2 deletion syndrome. In the toddler years, boys with KS may present with developmental delay, especially with expressive language skills [Walzer et al., 1978]. Mosaicism 46,XY/47,XXY generally results in both less severe clinical symptoms and endocrine abnormalities [Samplaski et al., 2014]. The 3-year-old boy had normal external genital development, which can be because of his young age and mosaicism. As KS is a common sex chromosomal aneuploidy, which is usually detected in the reproductive period when a person encounters infertility, it can be expected that the main phenotypic features of the patient will be those of the 10q microdeletion syndrome. This opinion is further supported by the fact that the symptoms of KS are much milder, especially when it comes to mosaicism.

The origin of this mosaicism is most likely postzygotic. Multiple chromosomal events, while rare, often include sex chromosome trisomy, which is relatively common and viable. This would suggest that, ontologically, the microdeletion appeared earlier than the aneuploidy for the X chromosome. The phenotype of patients with an LCR3/4-flanked 10q22.3q23.2 deletion can be rather variable, so counseling the families regarding the prognosis of an affected child should be done with caution. Long-term studies of affected children are needed to delineate the natural history of this rare disorder.

The identification of new cases will improve our understanding of the phenotyping spectrum associated with 10q22.3q23.2 microdeletions. The genotype-phenotype correlation will enable adequate genetic counseling.

Statement of Ethics

Written informed consent was obtained from the patient's parents for publication of this case report and any accompanying images.

The current report about the presented case was written in accordance with the guidelines of the Helsinki declaration. The current patient agreed to participate in the research and signed an informed consent form, and permission was obtained from the local Ethics Committee of Canakkale Onsekiz Mart University, Canakkale, Turkey, reference number 2013-163.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

Funding for this research was provided by Scientific Research Foundation Unit (BAP) of Canakkale Onsekiz Mart University, Canakkale-Turkey (Grant no: BAP-TAY2015/445).

Data Availability Statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Author Contributions

F.S., F.D.B., and M.B.A.: acquisition of data, analyzed the clinical data and designed the clinical experiments, designed the experiments, performed PCR, analyzed the sequencing data. F.D.B. and J.V.: software, validation, wrote the manuscript. O.O.: conceptualization, interpretation of data, supervised the study, and reviewed the manuscript. All authors read and approved the final manuscript.

Acknowledgement

The authors thank the family members who agreed to participate in the presented results.

References

  1. Balciuniene J, Feng N, Iyadurai K, Hirsch B, Charnas L, Bill BR, et al. Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with cognitive and behavioral abnormalities. Am J Hum Genet. 2007;80:938–47. doi: 10.1086/513607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breckpot J, Tranchevent LC, Thienpont B, Bauters M, Troost E, Gewillig M, et al. BMPR1A is a candidate gene for congenital heart defects associated with the recurrent 10q22q23 deletion syndrome. Eur J Med Genet. 2012;55((1)):12–6. doi: 10.1016/j.ejmg.2011.10.003. [DOI] [PubMed] [Google Scholar]
  3. Caldwell PD, Smith DW. The XXY (Klinefelter's) syndrome in childhood: detection and treatment. J Pediatr. 1972;80((2)):250–8. doi: 10.1016/s0022-3476(72)80586-9. [DOI] [PubMed] [Google Scholar]
  4. Coelho Molck M, Simioni M, Paiva Vieira T, Paoli Monteiro F, Gil-da-Silva-Lopes VL. A New Case of the Rare 10q22.3q23.2 Microdeletion Flanked by Low-Copy Repeats 3/4. Mol Syndromol. 2017;8((3)):161–7. doi: 10.1159/000469965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. D'Alessandro LC, Turki SA, Manickaraj AK, Manase D, Mulder BJ, Bergin L, et al. Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect. Genet Med. 2016;18((2)):189–98. doi: 10.1038/gim.2015.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Frühmesser A, Kotzot D. Chromosomal Variants in Klinefelter Syndrome. Sex Dev. 2011;5:109–23. doi: 10.1159/000327324. [DOI] [PubMed] [Google Scholar]
  7. Gaussin V, Van de Putte T, Mishina Y, C Hanks M, Zwijsen A, Huylebroeck D, et al. Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci U S A. 2002;99:2878–83. doi: 10.1073/pnas.042390499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Graham JM, Jr, Bashir AS, Stark RE, Silbert A, Walzer S. Oral and written language abilities of XXY boys: implications for anticipatory guidance. Pediatrics. 1988;81:795–806. [PubMed] [Google Scholar]
  9. Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet. 2001;28:184–7. doi: 10.1038/88919. [DOI] [PubMed] [Google Scholar]
  10. McGowan-Jordan J, Simons A, Schmid M. ISCN 2016: An International System for Human Cytogenomic Nomenclature. Cytogenet Genome Res. 2016;149:1–140. [Google Scholar]
  11. John MS, Ponchard C, van Reyk O, Mei C, Pigdon L, Amor DJ, et al. Speech and language in children with Klinefelter syndrome. J Commun Disord. 2019;78:84–96. doi: 10.1016/j.jcomdis.2019.02.003. [DOI] [PubMed] [Google Scholar]
  12. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter's syndrome. Lancet. 2004;364:273–83. doi: 10.1016/S0140-6736(04)16678-6. [DOI] [PubMed] [Google Scholar]
  13. Lupianez DG, Spielmann M, Mundlos S. Breaking TADs: how alterations of chromatin domains results in disease. Trends Genet. 2016;32((4)):225–37. doi: 10.1016/j.tig.2016.01.003. [DOI] [PubMed] [Google Scholar]
  14. Menko FH, Kneepkens CM, de Leeuw N, Peeters EA, Van Maldergem L, Kamsteeg EJ, et al. Variable phenotypes associated with 10q23 microdeletions involving the PTEN and BMPR1A genes. Clin Genet. 2008;74:145–54. doi: 10.1111/j.1399-0004.2008.01026.x. [DOI] [PubMed] [Google Scholar]
  15. Muro EM, Ibn-Salem J, Andrade-Navarro MA. The distributions of protein coding genes within chromatin domains in relation to human disease. Epigenetics Chromatin. 2019;12((1)):72. doi: 10.1186/s13072-019-0317-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nevado J, Mergener R, Palomares-Bralo M, Souza KR, Vallespín E, et al. New microdeletion and microduplication syndromes: a comprehensive review. Genet Mol Biol. 2014;37((Suppl 1)):210–9. doi: 10.1590/s1415-47572014000200007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Petrova E, Neuner C, Haaf T, Schmid M, Wirbelauer J, Jurkutat A, et al. A Boy with an LCR3/4-Flanked 10q22.3q23.2 Microdeletion and Uncommon Phenotypic Features. Mol Syndromol. 2014;5:19–24. doi: 10.1159/000355847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rego A, Coll MD, Regal M, Guitart M, Escudero T, García-Mayor RV. A case with 47,XXY,del(15)(q11;q13) karyotype associated with Prader-Willi phenotype. Horm Res. 1997;48((1)):44–6. doi: 10.1159/000185422. [DOI] [PubMed] [Google Scholar]
  19. Rodrigues MA, Morgade LF, Dias LFA, Moreira RV, Maia PD, Sales AFH, et al. Down-Klinefelter syndrome (48,XXY,+21) in a neonate associated with congenital heart disease. Genet Mol Res. 2017;16((3)) doi: 10.4238/gmr16039780. [DOI] [PubMed] [Google Scholar]
  20. Samango-Sprouse CA, Counts DR, Tran SL, Lasutschinkow PC, Porter GF, Gropman AL. Update on the clinical perspectives and care of the child with 47,XXY (Klinefelter Syndrome) Appl Clin Genet. 2019;12:191–202. doi: 10.2147/TACG.S180450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Samplaski MK, Lo KC, Grober ED, Millar A, Dimitromanolakis A, Jarvi KA. Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil Steril. 2014;101((4)):950–5. doi: 10.1016/j.fertnstert.2013.12.051. [DOI] [PubMed] [Google Scholar]
  22. Slavotinek AM. Novel microdeletion syndromes detected by chromosome microarrays. Hum Genet. 2008;124:1–17. doi: 10.1007/s00439-008-0513-9. [DOI] [PubMed] [Google Scholar]
  23. van Bon BW, Balciuniene J, Fruhman G, Nagamani SC, Broome DL, Cameron E, et al. The phenotype of recurrent 10q22q23 deletions and duplications. Eur J Hum Genet. 2011;19:400–8. doi: 10.1038/ejhg.2010.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Walzer S, Wolff PH, Bowen D, Silbert AR, Bashir AS, Gerald PS, et al. A method for the longitudinal study of behavioral development in infants and children: the early development of XXY children. J Child Psychol Psychiatry. 1978;19((3)):213–29. doi: 10.1111/j.1469-7610.1978.tb00465.x. [DOI] [PubMed] [Google Scholar]
  25. Williams A, Chandrashekar L, Srivastava VM, Thomas M, Horo S, George R. Incontinentia pigmenti, an X-linked dominant disorder, in a 2-year-old boy with Klinefelter syndrome. Indian J Pathol Microbiol. 2017;60((3)):424–6. doi: 10.4103/IJPM.IJPM_91_16. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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