Mosaic Klinefelter Syndrome Research Articles

Klinefelter syndrome in a patient with double Y-autosomal translocation

Klinefelter syndrome is one of the most common chromosomal abnormalities and the most common genetic cause of male infertility. About 85 % of patients have 47,XXY karyotype, other patients have other non-mosaic and mosaic Klinefelter syndrome variants. We report a unique clinical case — Klinefelter syndrome patient with double Y autosomal translocation. The proband is a 15-year-old male patient (height 180 cm, weight 50 kg, normal IQ) who was admitted for cytogenetic examination and genetic counseling due to delayed puberty. He was diagnosed with testicular hypoplasia, hypergonadotropic hypogonadism, pituitary microadenoma and left-sided varicocele. The proband was born in a nonconsanguineous marriage after in vitro fertilization due to paternal male factor infertility. Cytogenetic analysis was performed on cultured peripheral blood lymphocytes using standard chromosome analysis with GTG staining and FISH analysis. Molecular analysis of the Y chromosome was performed by multiplex PCR. Complex cytogenetic examination revealed a 46,XX,der(Y) t(Y;15)(q12;q11.1),der(13)t(Y;13)(q12;p11.2),-15 karyotype in the proband. Molecular analysis showed that the proband is SRY positive; no microdeletion of the Y chromosome was found. The detected double Y autosomal translocation is a chromosomal abnormality independent of KS. The father of the proband is an oligozoospermic man with robertsonian translocation 13;15 — 45,XY,der(13;15)(q10;q10), the mother has a normal karyotype 46,XX. Apparently, the der(13) and der(Y) chromosomes result from abnormal meiotic recombination in paternal meiosis between the heterochromatic region Yq12 and the centromeric/pericentromeric heterochromatin of chromosomes 13 and 15 involved in the paternal robertsonian translocation, and Klinefelter syndrome is due to the presence of two X chromosomes in the karyotype in the presence of a derivative Y chromosome. The detected double Y-autosomal translocation is a chromosomal abnormality unrelated to Klinefelter syndrome, arising on the background of the paternal robertsonian translocation.

Klinefelter Syndrome: A Genetic Disorder Leading to Neuroendocrine Modifications and Psychopathological Vulnerabilities in Children-A Literature Review and Case Report.

Klinefelter syndrome (KS), characterized by an additional X-chromosome in males, manifests in a wide range of neuroendocrine and psychiatric symptoms. Individuals with KS often face increased risks of hormonal dysfunction, leading to depression and anxiety, although extended research during pediatric and adolescent age is still limited. This critical phase, decisive for KS children, is influenced by a combination of genetic, environmental and familial factors, which impact brain plasticity. In this report, we reviewed, in a narrative form, the crucial KS psychopathological hallmarks in children. To better describe neuroendocrine and neuropsychiatric outcomes in children with KS, we presented the case of an 11-year-old prepubertal child with mosaic KS who was referred to our Center of Developmental Psychopathology due to a decline in his academic performance, excessive daytime fatigue and increased distractibility over the past few months. Family history revealed psychiatric conditions among first- and second-degree relatives, including recently divorced parents and a 15-year-old sister. Early-onset persistent depressive disorder and anxious traits were diagnosed. Timely identification of susceptible children, with thorough examination of familial psychiatric history, environmental influences and neurocognitive profile, alongside targeted interventions, could potentially mitigate lifelong psychopathology-related disabilities in pediatric and adolescent KS cases, including those with mosaic KS.

Differences in clinical outcomes between men with mosaic Klinefelter syndrome and those with non-mosaic Klinefelter syndrome.

This study compared the clinical outcomes of men with Klinfelter syndrome based on karyotype. The authors analyzed the outcomes of microdissection testicular sperm extraction (micro-TESE) performed on 57 patients with Klinfelter syndrome (KS) at our clinic. The average ages of the non-mosaic and mosaic KS groups were 32.2 ± 4.8 and 45.9 ± 13.1 years, respectively. The sperm retrieval rates of the non-mosaic and mosaic KS groups were 46.5% (20/43) and 50.0% (7/14), respectively. The fertilization rates after intracytoplasmic sperm injection did not significantly differ between the non-mosaic and mosaic KS groups. The mosaic KS group had higher cleavage and blastocyst development rates than the non-mosaic KS group (72.2% vs. 96.2% and 30.5% vs. 44.7%, respectively). The group using motile sperm had better outcomes than the group using immotile sperm. The embryo transfer outcomes of the non-mosaic and mosaic KS groups did not significantly differ (clinical pregnancy rate: 28.0% vs. 20.7%, miscarriage rate: 14.3% vs. 33.3%, production rate per transfer: 22.0% vs. 13.8%, and production rate per case: 58.8% vs. 57.1%). Compared with the non-mosaic KS group, the mosaic KS group had significantly better intracytoplasmic sperm injection outcomes because of the higher utilization rate of motile sperm.

O-140 studying the effect of mosaicism on the outcome of micro-TESE among Klinefelter syndrome patients

Abstract Study question Does mosaicism affect sperm retrieval rate in Klinefelter patients? Summary answer Patients with mosaic Klinefelter syndrome (KS) have a higher success rate of sperm retrieval than those with non-mosaic KS. What is known already Klinefelter syndrome is characterised by the presence of an extra X chromosome in male individuals leading to a 47XXY karyotype and rarely to 46XY/47XXY Mosaicism; it is the most common sex chromosomal aneuploidy and the most common genetic cause of Azoospermia (Kanakis GA et al., 2018 and Gravholt CH et al.,2018). It accounts for 3–4% of male infertility cases and 10–12% of men with Azoospermia (Winters SJ,2018). Study design, size, duration After approval of the ethical committee of the faculty of medicine at Cairo University, This prospective study was conducted where 70 men who complained of primary infertility and azoospermia and were diagnosed with Klinefelter Syndrome were recruited for this study between 1/11/2021 and 30/11/2022. Patients with previous testicular disease (torsion, trauma) or who had a history of undescended testes or received chemotherapy or radiotherapy were excluded. Participants/materials, setting, methods Seventy patients (n = 70) aged between 20 and 50 who fit the inclusion criteria were recruited and underwent micro_TESE. Semen analysis (Azoospermia), hormonal profile, scrotal colour doppler ultrasonography, Karyotyping and FISH for Y and X chromosomes were performed. Statistical analysis was conducted using SPSS 22nd edition. Main results and the role of chance Our study groups comprised 14 patients with mosaic KS and 56 with non-mosaic KS. The clinical characteristics were not significantly different statistically between the two groups. Micro_TESE was performed in all 70 patients; in 26 patients (37.1%), mature sperm were found in the wet preparation. No statistically significant correlation was found between the presence of spermatozoa in the extraction specimen and age, serum follicle-stimulating hormone, serum testosterone, prolactin or oestradiol. The statistically significant predictor variable for sperm extraction was mosaicism, luteinising hormone, testicular volume and FISH. The sperm retrieval rate of the patients with mosaic and non-mosaic KS was 57.1% and 32.1%, respectively. Limitations, reasons for caution 1) Larger (n) number of patients was needed. 2) Despite our valuable findings, further studies should be performed to illuminate the relation between FISH for X and Y chromosomes and sperm retrieval rate success. Wider implications of the findings Klinefelter patients with mosaicism should be offered high sperm retrieval rate during IVF counselling. Trial registration number n/a

Late-discovered mosaic Klinefelter syndrome with severe osteoporosis and obesity

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Clinical and laboratory differences between chromosomal and undefined causes of non-obstructive azoospermia: A retrospective study.

Knowledge of clinical and laboratory differences between chromosomal and undefined causes aids etiological research on non-obstructive azoospermia. Compare clinical and laboratory differences between men with non-obstructive azoospermia due to chromosomal anomalies versus undefined causes. A cross-sectional retrospective study conducted at a public university hospital in Campinas (Brazil). All men aged 20-40 years with non-obstructive azoospermia were included in the analysis. The 107 cases included 14 with Klinefelter syndrome (KS) (13%), 1 with mosaic KS, 4 with sex development disorders (2 testicular XX, 1 NR5A1 gene mutation, and 1 mild androgen insensitivity syndrome) (4%), 9 with other non-obstructive azoospermia etiologies (8%), and 79 with undefined causes. The 22 chromosomal anomaly cases (14 KS, 1 mosaic KS, 2 testicular XX, 4 sex chromosome anomalies, and 1 autosomal anomaly) were compared with the 79 undefined cause cases. The KS group had lower average testicular volume, shorter penile length, and lower total testosterone levels but greater height, arm span, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and gynecomastia frequency (absent in the undefined group and affecting more than half of the KS group). Patients with testicular XX DSD had LH, FSH, and penile length data intermediate between the KS and undefined cause groups, testicular volume similar to the KS group, and other data similar to the undefined group. Clinical and laboratory data differentiate men with non-obstructive azoospermia and chromosomal anomalies, particularly KS and testicular XX, from those with undefined causes or other chromosomal anomalies.

Retrospective analysis of the sex chromosomal copy number variations in 186 fetuses using single nucleotide polymorphism arrays.

Sex chromosomal abnormalities are associated with multiple defects. However, the types of sex chromosomal abnormalities during pregnancy in Fujian Province, China, are not recorded. In this retrospective analysis, we showed the sex chromosomal abnormalities of 186 fetuses, including 162 cases of X chromosomal abnormalities and 22 cases of Y chromosomal abnormalities in Fujian Province. We detected 73 cases of Turner syndrome, 24 cases of triple X syndrome, 37 cases of Klinefelter syndrome, and 14 cases of XYY syndrome. It was observed that 67.3% fetuses with classic Turner syndrome had their growth arrested. Moreover, we found 21 cases of mosaic Turner syndrome, 3 cases of mosaic Triple X syndrome, 2 cases of mosaic Klinefelter syndrome, and 1 case of mosaic XYY syndrome. Furthermore, 37 cases of large scales of sex chromosomal deletions/duplications were detected, including 30 cases of X chromosomal deletions/duplications and 7 cases of Y chromosomal deletions/duplications. Parent-of-origins of five cases of sex chromosomal deletions/duplications were determined. One case was with de novo X chromosomal variations, while the sex chromosomal deletions/duplications in other four cases were inherited from their parents. Overall, our results presented a detailed manifestation of sex chromosomal abnormalities of 186 fetuses in Fujian Province and suggested the important roles of single nucleotide polymorphism (SNP) array analysis in the prenatal diagnosis of sex chromosomal abnormalities. Also, determining the parent-of-origins of the deletions/duplications was critical for the prenatal diagnosis of sex chromosomal abnormalities.

Modeling sex differences in humans using isogenic induced pluripotent stemcells.

Biological sex is a fundamental trait influencing development, reproduction, pathogenesis, and medical treatment outcomes. Modeling sex differences is challenging because of the masking effect of genetic variability and the hurdle of differentiating chromosomal versus hormonal effects. In this work we developed a cellular model to study sex differences in humans. Somatic cells from a mosaic Klinefelter syndrome patient were reprogrammed to generate isogenic induced pluripotent stem cell (iPSC) lines with different sex chromosome complements: 47,XXY/46,XX/46,XY/45,X0. Transcriptional analysis of the hiPSCs revealed novel and known genes and pathways that are sexually dimorphic in the pluripotent state and during early neural development. Female hiPSCs more closely resembled the naive pluripotent state than their male counterparts. Moreover, the system enabled differentiation between the contributions of X versus Y chromosome to these differences. Taken together, isogenic hiPSCs present a novel platform for studying sex differences in humans and bear potential to promote gender-specific medicine in the future.

Late-discovered mosaic Klinefelter syndrome with severe osteoporosis and obesity

Late-discovered mosaic Klinefelter syndrome with severe osteoporosis and obesity

34. A rare case of 46,XX/47,XXY mosaic Klinefelter syndrome in an infant

Klinefelter syndrome is a sex chromosome disorder that occurs in approximately 1 in 600 males and is classically characterized by a 47,XXY karyotype. Patients generally present in adolescence or adulthood with gynecomastia, learning difficulties, developmental delay, hypergonadtropic hypogonadism, infertility, tall stature, and behavioral problems. Mosaic Klinefelter syndrome, found in roughly 10% of cases, is typically associated with a 47,XXY/46,XY karyotype; however, there are a few (<20) reported cases of 47,XXY/46,XX karyotype. These individuals often possess both testicular and ovarian tissues that can occur in the same gonad or separately. Here, we report on a 20-month-old (assigned male at birth) who presented to neurology with motor delay and hypotonia. Clinic notes mentioned an earlier diagnosis of mosaic Klinefelter syndrome, although no records were available for review. Cytogenetic and microarray analysis in our laboratory revealed a mosaic karyotype with 47,XXY in 15 cells and 46,XX in 5 cells. Microarray and FISH studies confirmed 82% 47,XXY and 18% 46,XX. Endocrine studies are consistent with testicular gonadal tissue and hormone levels suggest normal gonadal function. Testosterone level and thyroid function were both normal for his age. A pelvic ultrasound identified normal-appearing testicles and no evidence of a uterus or fallopian tube structures. The patient will continue to be followed by neurology and endocrinology. Clinical management of patients with differences in sex development (DSDs) is challenging and given the rarity of this chromosomal finding and highly variable reported phenotype of patients, it is difficult to predict the clinical phenotype for this patient. This case highlights the complexity in those presenting with DSDs and the need for further studies on individuals with similar findings.

Micro-dissection testicular sperm extraction in Klinefelter's syndrome patients, King Faisal Specialist Hospital and Research Center, Riyadh experience.

Background:In Klinefelter's syndrome patients with azoospermia, microscopic testicular sperm extraction (m-TESE) can be proposed as a therapeutic option.Aim of Study:The aim of this study is to assess the sperm retrieval rate in patients with Klinefelter syndrome in King Faisal Specialist Hospital, Riyadh.Methodology:Retrospective, Chart review of 32 patients with Klinefelter syndrome who underwent m-TESE were reviewed and analyzed. All patients had two sets of semen analysis after 3 − 5 days abstinence of ejaculation with further study of semen by in vitro fertilization (IVF) wash. The hormonal analysis was studied. Ultrasonography of testes was assessed preoperatively. Testicular tubules were sent to the IVF laboratory and were studied under the microscope looking for sperms. Some testicular tissues were sent for the histopathology diagnosisResults:Patients’ mean age was 34.9 ± 6.0 years. Mean hormonal levels of E2, FSH, LH, prolactin, and testosterone were 96.0 ± 22.0 pmol/L, 29.8 ± 5.4 IU/L, 19.0 ± 2.9 IU/L, 15.4 ± 3.6 ug/L, and 10.0 ± 1.9 nmol/L, respectively. There were two mosaic Klinefelter syndrome patients (6.25%), whereas 30 patients had a nonmosaic form (93.75%). The overall sperm retrieval rate was 37.5%. All patients had small bilateral testes. Sperm retrieval was successful in three patients with hypospermatogenesis, one patient with maturation arrest, and 8 patients with Sertoli-cell-only pattern. Four patients with complete hyalinization of testicular tissues had complete failure to retrieve sperms. The pregnancy rate after intra-cytoplasmic sperm injection was 50%.Conclusions:The sperm retrieval rate in Klinefelter syndrome patients with m-TESE is in accordance with most of those reported in the literature. Regarding histopathology, hypo-spermatogenesis showed a favorable outcome. The pregnancy rate with intra-cytoplasmic sperm injection was 50%.

Andrological and cytogenetic investigations of an infertile Przewalski's stallion.

The case of an 8-year-old, sexually active but infertile Przewalski's stallion (Equus ferus przewalskii) was studied. Besides the infertility, the stallion also showed permanent problems with its body condition, being obviously weaker than all the other group members. The horse was kept in a separate place for two years with 12 mares in its harem group (six mares had foals earlier); however, none of the mares covered got pregnant. Andrological and cytogenetic investigations revealed underdeveloped testes, arrested spermatogenesis, azoospermia, and XY/XXY/X0 mosaicism. We classify the case as a mosaic Klinefelter syndrome, the first reported case in Przewalski's horse.

An ultra-rare case of 47,XXY/48,XXXY/49,XXXXY mosaic Klinefelter syndrome associated with diabetic ketosis and foot ulcer

Klinefelter syndrome (KS) is the most common chromosome aneuploidy and a common cause of infertility in males. KS patients have at least one extra X chromosome, and about 80% of patients have the karyotype 47,XXY. Twenty percent of KS patients have higher-grade aneuploidies (48,XXXY, 48,XXYY, 49,XXXXY) and exert some clinical manifestation different from those with 47,XXY. Here we report the case of a young man who initially presented with diabetic ketosis and foot ulcer and was later diagnosed as having an extremely rare mosaic variant of KS (47,XXY/48,XXXY/49,XXXXY). Clinical and laboratory features are summarized. The patient developed a severe foot ulcer with an 18-month history of diabetes. Learning disability was noted since early childhood. The patient had typical manifestations of KS, including increased height, sparse beard and body hair, and small penis. He also had some characteristic features of patients with additional sex chromosomes, including epicanthal folds, narrow palpebral fissures, prominent elbows, and undescended testicles. Severe myopia and myopic macular degeneration was also found. Lab tests revealed low testosterone and elevated FSH but normal LH levels. Chromosome analysis on lymphocytes revealed an aberration of 47,XXY/48,XXXY/49,XXXXY. This case provides information on KS patients with the extremely rare karyotype 47,XXY/48,XXXY/49,XXXXY, and also emphasizes the importance of considering KS in the differential diagnosis of a sterile male with diabetes.

Chronic refractory leg ulcers in mosaic Klinefelter's syndrome: the importance of a prompt diagnosis and appropriate treatment.

Chronic refractory leg ulcers in mosaic Klinefelter's syndrome: the importance of a prompt diagnosis and appropriate treatment.

952 Prenatal phenotype of 47,XXY (Klinefelter syndrome)

The phenotypic description of prenatal Klinefelter syndrome (KS), or 47,XXY, is currently limited to case reports. There is a gap in knowledge regarding prenatal presentation of KS. We hypothesize that a significant percentage of pregnancies complicated by fetal KS will have associated ultrasonographic findings. We retrospectively identified all fetuses with cytogenetically confirmed 47,XXY in the prenatal period or up to age 5 years, with prenatal records available for review from four prenatal diagnostic referral centers between 2006 and 2019. Ultrasound reports were reviewed to assess for the presence of increased nuchal translucency (NT) and abnormalities at the second trimester anatomy ultrasound. Additionally, we reviewed results of cell free DNA and serum analyte testing to inform our understanding of prenatal screening tests in the setting of fetal KS. A total of 42 subjects with confirmed cytogenetic diagnosis of 47,XXY and prenatal records available for review were identified: 38 had a prenatal diagnosis of KS and 4 had a postnatal diagnosis. One case was excluded as cytogenetic analysis demonstrated mosaic KS, leaving a cohort of 41 subjects. NT was increased ≥3.0mm in 6 of 26 (23.1%) of cases that had a documented measurement. A second trimester anatomical survey was available for review in 24/41 affected pregnancies. In 7 of 24 (29.2%) ultrasounds, a fetal abnormality was identified. These include 3 brain anomalies, 1 cardiac abnormality, 1 echogenic bowel, and 2 limb abnormalities (table). In subjects who had cell free DNA performed, 92.6% had a positive result for 47,XXY (25/27); in subjects who had serum analytes performed, 36.3% (4/11) had a positive result. This case series expands our knowledge of the prenatal presentation of KS by identifying 1st and 2nd trimester fetal sonographic abnormalities as well as serum analyte abnormalities.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Derivation of two naturally isogenic iPSC lines (KAUSTi006-A and KAUSTi006-B) from a mosaic Klinefelter Syndrome patient (47-XXY/46-XY).

While Klinefelter Syndrome (KS) has a prevalence of 85-250 per 100,000 born males, patients are typically underdiagnosed due to a subtle phenotype emerging only late during puberty or adulthood. Rare cases of KS carry a mosaic phenotype 47-XXY/46-XY associated to mild phenotypic traits mostly compatible with a normal life including preserved fertility. From a genetic modeling perspective, the derivation of naturally isogenic iPSCs from mosaic patients allows the comparison of disease and healthy cells carrying a virtually identical genomic background.

Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review.

Most cases of Klinefelter syndrome (KS) have 47,XXY karyotype. We reported the first case of 46,XX/47,XXY KS whose genital ambiguity was detected prenatally with postnatal confirmation of the mosaicism and ovotesticular disorder of sex development (OT-DSD). The paternal origin of the extra X chromosome was identified using trio cytogenomic single-nucleotide polymorphism array. Additional 18 cases were also reviewed. The clinical presentation of 46,XX/47,XXY is age-dependent with two age peaks, including ambiguous genitalia during infancy and gynecomastia with or without cyclical hematuria and left scrotal pain and mass in adolescence. The 46,XX is the predominant karyotype both in peripheral blood and gonadal tissue. The risk of germ cell tumor is very high throughout life in these individuals. Individuals with 46,XX/47,XXY mosaicism should be treated more as OT-DSD other than a simple mosaic KS. A multidisciplinary approach and long-term monitoring are necessary.

Detection of low-grade mosaicism and its correlation with hormonal profile, testicular volume, and semen quality in a cohort of Egyptian Klinefelter and Klinefelter-like patients

Klinefelter syndrome (KS) is the most common chromosomal syndrome, causing infertility in men and leading to non-obstructive azoospermia. Previous studies on mosaicism have shown contradictory results on its correlation with both serum hormone levels and the presence of spermatozoa in the ejaculate of KS, KS-like, and non-KS-like infertile patients. So, the present study was designed to detect low-grade mosaicism in the peripheral blood lymphocytes and buccal mucosa cells of 14 KS and 8 KS-like patients by using fluorescence in situ hybridization (FISH) and to investigate its correlation with luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) levels, testicular volume, and semen analysis compared with 10 normal healthy fertile men. Our results indicated that mosaicism was only found in 42.9 % of the KS patients and completely absent in all KS-like patients. Moreover, mosaicism has led to complete azoospermia and non-significant differences in both hormone levels and testicular volume between mosaic and non-mosaic KS patients. All KS patients demonstrated significant differences in both hormone levels and testicular volume compared with normal men. Conversely, they revealed non-significant differences in hormone levels and significant differences in testicular volume compared with KS-like patients. Additionally, the KS-like patients exhibited non-significant variations in both LH and FSH levels and significant variations in T level and testicular volume compared with normal men. Moreover, all KS-like patients had azoospermia, except for one patient who showed oligozoospermia. Therefore, no correlations were found either between mosaicism and serum hormone levels or with testicular volume and semen analysis.

Spermatological characteristics of mosaic and non-mosaic forms of Klinefelter syndrome

The study objectiveis to compare of ejaculate parameters in mosaic, non-mosaic Klinefelter syndrome (KS).Materials and methods. Eighty-five patients with KS were examined. The group 1 included 75 patients between the ages of 17 and 39 with non-mosaic KS (47,XXY), the group 2 included 10 males between the ages of 22 and 57 years with mosaic KS: 47,XXY/46,XY (n = 9), 48,XXY,der(X)/47,XXY/46,XY (n = 1).Results. KS patients semen volume was 1.9 ± 1.3 (0.1–5.5) ml in non-mosaic KS patients (47,XXY) and 1.5 ± 1.2 (0.05–4.00) ml in patients with a mosaic form of a KS, respectively, рН semen – 7.8 ± 0.5 (6.5–9.0) and 7.8 ± 0.2 (7.5–8.1), sperm count – 0.27 ± 1.42 (0.00–12.50) and 0.12 ± 0.28 (0.00–0.90) million/ml, respectively. The viscosity was increased (&gt;20 mm) at 41 % non-mosaic KS (group 1) and 22 % of mosaic KS (group 2) patients. The ejaculate sediment was investigated by quantitative karyological analysis of immature germ cells. The germ cells in 42 % samples of the ejaculate of the patients with a classical form of a KS and in 20 % samples of the ejaculate of the patients with a mosaic form was found. That indicates a partial preservation of spermatogenesis.Conclusion. The degree of spermatogenesis depletion in KS patients widely varied, ejaculate and germ cell parameters in the ejaculate sediment weren’t significantly different. Presence of few sperms (cryptozoospermia) and immature cells in the ejaculate sediment point to partial preservation of spermatogenesis.

Congenital pulmonary airway malformation associated with mosaic Klinefelter syndrome

A 26-year-old female, G4 P2012 presented for an anatomy scan at 18 weeks. Multiple macrocysts were seen in the left fetal lung, which lead to a diagnosis of congenital pulmonary airway malformation (CPAM) type II. A fetal MRI examination performed at 24 weeks of gestation confirmed the diagnosis of CPAM type II. A genetic amniocentesis was done to rule out a fetal chromosomal abnormality and the fetus was found to have mosaic Klinefelter syndrome. Fetal CPAM is not usually associated with chromosomal abnormalities unless there are other fetal malformations present. This is the first known case where a fetus with CPAM and no other malformation was found to have mosaic Klinefelter syndrome. Therefore, we believe it is prudent to offer prenatal diagnostic testing whenever a fetus with CPAM is identified with ultrasound.