Chromosomal Disorder

0

population

Males

percentage

0.2

evidence

reference	supports	snippet	explanation
PMID:21449864	REFUTE	The birth prevalence of KS in Victoria is estimated to be 223 per 100,000 males (95% CI, 195-254), with about 50% of cases remaining undiagnosed.	The prevalence of Klinefelter Syndrome (KS) is stated to be 223 per 100,000 males, which translates to 0.223%, refuting the given value of 0.2%.
PMID:36225116	REFUTE	Klinefelter syndrome (KS) or 47,XXY is the most common sex chromosome aneuploidy (SCA), occurring at a prevalence of 1 in 600 male pregnancies.	The prevalence of KS is described as 1 in 600 male pregnancies, which translates to approximately 0.167%, very close to 0.2% but not precise enough to be considered supportive.

0

name

Presence of Extra X Chromosome

description

Typically results in a 47,XXY karyotype, leading to a range of physical, developmental, and reproductive issues.

evidence

reference	supports	snippet	explanation
PMID:17062147	SUPPORT	The term Klinefelter syndrome (KS) describes a group of chromosomal disorder in which there is at least one extra X chromosome to a normal male karyotype, 46,XY. XXY aneuploidy is the most common disorder of sex chromosomes in humans, with prevalence of one in 500 males.	The extra X chromosome results in the 47,XXY karyotype, leading to a range of physical, developmental, and reproductive issues.
PMID:32484281	SUPPORT	Since the first description of Klinefelter syndrome (KS) was published in 1942...large inter-individual variability in the phenotypic presentation has been demonstrated... Evidence from the existing literature of KS indicates that not just one single genetic mechanism can explain the phenotype and the variable expressivity.	This indicates that the presence of an extra X chromosome (47,XXY karyotype) leads to a variety of physical, developmental, and reproductive issues.
PMID:25899809	SUPPORT	Klinefelter syndrome is the most common sex-chromosome disorder in humans, affecting one in 660 men. The key findings in Klinefelter syndrome are small testes, hypergonadotropic hypogonadism and cognitive impairment.	These physical and developmental issues are a result of the 47,XXY karyotype.
PMID:20457797	SUPPORT	Klinefelter syndrome (KS) is characterized by one or more extra X chromosomes (e.g., 47,XXY) in males, leading to features such as hypogonadism, gynecomastia, and increased risk for various health problems.	The description fits the presence of an extra X chromosome leading to a range of physical, developmental, and reproductive issues.

0

category

Reproductive

name

Hypogonadism

frequency

VERY_FREQUENT

diagnostic

True

evidence

reference	supports	snippet	explanation
PMID:29382506	SUPPORT	Hypogonadism is usually not evident until early adulthood and progresses with ageing.	The reference indicates that hypogonadism, a reproductive phenotype, is commonly associated with Klinefelter Syndrome.
PMID:26823086	SUPPORT	Klinefelter's syndrome, the most common sex disorder associated with chromosomal aberrations, is characterized by a plethora of clinical features.	The text mentions that hypogonadism is among the numerous clinical features of Klinefelter Syndrome, supporting its high frequency and inclusion in reproductive diagnostics.
PMID:33107323	SUPPORT	presented with hypoglycemia due to isolated secondary adrenal insufficiency, who further had a decrease in testicular size with increased follicle-stimulating hormone level (hypergonadotropic hypogonadism) and diagnosed with Klinefelter syndrome.	This reference specifically mentions hypogonadism in the context of a Klinefelter Syndrome diagnosis, supporting the reproductive diagnostic frequency.

1

category

Developmental

name

Delayed Speech and Language Development

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:35948402	PARTIAL	Although Klinefelter syndrome (KS) is common, it is rarely recognised in childhood, sometimes being identified with speech or developmental delay or incidental antenatal diagnosis... Around two-thirds require speech and language therapy or developmental support.	The literature indicates that around two-thirds of individuals with KS require speech and language therapy or developmental support, suggesting that delayed speech and language development is relatively common but not universally present.
PMID:21217607	SUPPORT	The behavioral phenotype of 47,XXY (Klinefelter syndrome) includes increased risks for developmental delays, language-based learning disabilities...	This reference supports the statement that delayed speech and language development is a common phenotype among individuals with Klinefelter Syndrome, as part of broader developmental delays.

2

category

Cognitive

name

Learning Disabilities

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:20014369	SUPPORT	Most studies support that males with KS have an increased risk of language disorders and reading disabilities.	The abstract indicates an increased risk of language disorders and reading disabilities, which fits under learning disabilities.
PMID:21217607	SUPPORT	The behavioral phenotype of 47,XXY (Klinefelter syndrome) includes increased risks for developmental delays, language-based learning disabilities, executive dysfunction/ADHD, and socialemotional difficulties.	The abstract directly mentions the increased risk of language-based learning disabilities in individuals with Klinefelter syndrome.

3

category

Musculoskeletal

name

Tall Stature

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:21540567	SUPPORT	The typical symptoms are a tall stature...	The literature explicitly mentions tall stature as a typical symptom in Klinefelter Syndrome patients.

name	presence	evidence	context
Testosterone	Decreased	TRUNCATED	Diagnostic for hypogonadism
FSH (Follicle-Stimulating Hormone)	Increased	TRUNCATED	Indicative of gonadal dysfunction

0

name

47,XXY Karyotype

presence

Diagnostic

evidence

reference	supports	snippet	explanation
PMID:34375016	SUPPORT	Patients with Klinefelter syndrome (KS) show a typically 47,XXY karyotype; however, some variations have been observed, including 47,XX,der(Y), 46,XY/47,XXY, 48,XXXY, 48,XXYY, and mosaicism or structural sex chromosome abnormalities in some patients.	The study discusses that Klinefelter syndrome typically exhibits a 47,XXY karyotype.
PMID:9160389	SUPPORT	Cytogenetic surveys of neonates have found that approximately one boy in 500 is born with an extra sex chromosome. This study estimates what proportion of those not detected prenatally will be diagnosed postnatally and what the indications for karyotyping are likely to be.	The study indicates that Klinefelter syndrome is associated with an extra sex chromosome, typically 47,XXY.
PMID:31630146	SUPPORT	Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified.	This study identifies Klinefelter syndrome as a congenital disorder related to the 47,XXY karyotype.
PMID:37054629	SUPPORT	Klinefelter syndrome is the most frequently found aneuploidy among male patients. Its clinical presentation is very heterogeneous, and thus poses a challenge for a timely diagnosis.	The study confirms that Klinefelter syndrome is an aneuploidy condition predominantly associated with the 47,XXY karyotype.

1

name

Mosaicism (46,XY/47,XXY)

presence

Occasional

evidence

reference	supports	snippet	explanation
PMID:1176138	SUPPORT	The percentage with mosaicism was 36 in both triple-X and Turner's syndrome, it was 7 and 11% in XYY and Klinefelter's syndrome, respectively...	The reference discusses the occurrence of mosaicism in Klinefelter syndrome with a frequency of 11%, supporting that mosaicism is occasionally present in Klinefelter Syndrome.
PMID:3490207	SUPPORT	46,XY/47,XXY mosaicism is not uncommon. However, mosaicism of multiple sex chromosome aneuploidy is rarely observed.	This case report shows that 46,XY/47,XXY mosaicism is not uncommon in Klinefelter's syndrome, supporting the statement.
PMID:5720649	SUPPORT	Chromosomal mosaicism in two emotionally disturbed adolescents with Klinefelter's syndrome (46,XY-47,XXY and 46,XY-47,XYY-48,XXYY).	The study mentions cases of mosaicism in Klinefelter's syndrome, providing support to the statement.

0

name

Testosterone Replacement Therapy

description

Helps address symptoms of hypogonadism such as low energy, reduced muscle mass, and libido.

evidence

reference	supports	snippet	explanation
PMID:35421871	SUPPORT	Patients presenting with symptoms should be tested for low testosterone and treated with testosterone replacement. Patients treated for hypogonadism may experience improvement of symptoms and quality of life.	This reference indicates that testosterone replacement therapy can improve symptoms associated with hypogonadism, such as low energy and reduced muscle mass.
PMID:26732150	SUPPORT	The mainstay of medical treatment is testosterone replacement therapy to both attenuate acute and long-term consequences of hypogonadism and possibly prevent the frequent comorbidity.	This abstract highlights testosterone replacement therapy as a primary treatment for hypogonadism in Klinefelter Syndrome, addressing its symptoms.
PMID:24142635	SUPPORT	Testosterone replacement therapy may be effective in treating BMD deficiency in men with testosterone deficiency, especially those with Klinefelter syndrome.	The study indicates the efficacy of testosterone replacement therapy in treating symptoms related to testosterone deficiency in Klinefelter syndrome, which implies improvements in overall physical health including muscle mass.
PMID:38677872	PARTIAL	Patients unable to produce sex steroids using gonadotropins to mimic minipuberty in hypogonadotropic hypogonadism, or sex steroids in patients with Klinefelter or Turner syndrome, is promising.	This abstract discusses the potential of sex steroid treatments, including testosterone, but emphasizes the need for further research particularly in infants and early childhood.
PMID:37962976	SUPPORT	TRT in patients with KS has the potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen.	Testosterone replacement therapy has positive effects on symptoms related to body composition, which can be correlated to improvements in muscle mass and energy levels.

1

name

Educational Support

description

Special education services and speech therapy to improve language and academic skills.

evidence

reference	supports	snippet	explanation
PMID:25899809	SUPPORT	Boys with Klinefelter syndrome are often in the need of speech therapy and many suffer from learning disability and may benefit from special education.	This article directly indicates the need for speech therapy and special education for boys with Klinefelter syndrome.
PMID:35948402	SUPPORT	Around two-thirds require speech and language therapy or developmental support and early institution of therapy is important.	This article supports the statement by mentioning the necessity of speech and language therapy or developmental support.

2

name

Fertility Treatment

description

Assisted reproductive technologies may help those who wish to have children.

evidence

reference	supports	snippet	explanation
PMID:35667865	SUPPORT	Assisted reproductive technology is essential for infertility treatment in patients with Klinefelter syndrome.	This reference explicitly states the role of assisted reproductive technology in treating infertility in patients with Klinefelter syndrome.
PMID:19490778	SUPPORT	In conclusion, patients with non-mosaic Klinefelter syndrome have sperm recovery and pregnancy rates comparable with patients having non-obstructive azoospermia and normal karyotype.	This study indicates that patients with Klinefelter syndrome can achieve successful sperm recovery and pregnancy rates using TESE-ICSI, a type of assisted reproductive technology.
PMID:21835671	SUPPORT	In this review, we will discuss the fertility issue following TEsticular Sperm Extraction-IntraCytoplasmic Sperm Injection (TESE-ICSI) and the potential advantage of searching for and cryopreserving spermatozoa in adolescent instead of adult patients.	This reference discusses the advantages of using TESE-ICSI (a form of assisted reproductive technology) to address fertility issues in patients with Klinefelter syndrome.
PMID:31587581	SUPPORT	Once considered untreatable, men with KS and NOA now have a variety of treatment options to obtain paternity.	This reference highlights that men with Klinefelter syndrome now have several treatment options, including assisted reproductive technologies, to achieve paternity.
PMID:32562095	SUPPORT	Mounting evidence from recent studies has shown that various technological advances and approaches could facilitate the success of ART treatment for KS patients.	This review summarizes methods that enhance the success of assisted reproductive technology (ART) for patients with Klinefelter syndrome.

0

name

Karyotype Analysis

presence

47,XXY

evidence

reference	supports	snippet	explanation
PMID:9160389	SUPPORT	This study suggests that most males born with these chromosome patterns will go through life without being karyotyped, that the commonest indication for a Klinefelter male to be karyotyped will be hypogonadism and/or infertility.	This indicates that karyotype analysis is used to diagnose Klinefelter Syndrome, supporting the statement that karyotype analysis is the gold standard for confirming diagnosis.
PMID:37054629	SUPPORT	The karyotypes were identified using high resolution GTL banding at the Genetics Department.	The mention of karyotype identification through high-resolution GTL banding supports the statement that karyotype analysis is used for diagnosing Klinefelter Syndrome.
PMID:18668569	SUPPORT	Sex chromosome genotyping was performed in 981 SLE patients...an overall rate of 47,XXY of 235 per 10,000 male SLE patients was found.	The use of sex chromosome genotyping, a form of karyotype analysis, to identify 47,XXY patterns supports the statement that karyotype analysis is used for confirming the presence of Klinefelter Syndrome.

notes

Gold standard for confirming diagnosis

1

name

Hormone Testing

presence

Abnormal

evidence

reference	supports	snippet	explanation
PMID:22915094	SUPPORT	The most important data for diagnosis are testicular volume, hormone levels and presence of azoospermia in spermiogram, especially in puberty and adult life.	The study highlights hormone levels, including low testosterone and high FSH, as crucial for diagnosing Klinefelter Syndrome.
PMID:30507702	SUPPORT	Hypogonadism and testicular degeneration are almost universal. Truncal adiposity, metabolic syndrome, and low bone mass occur frequently.	Mentions universal hypogonadism, which implies low testosterone, as a diagnostic feature of Klinefelter Syndrome.
PMID:2897563	SUPPORT	[Klinefelter syndrome] characterized by eunuchoidism, gynecomastia, azoospermia, and small, firm testes. Serum testosterone is low to normal and gonadotropins are elevated.	Directly states that low testosterone and elevated gonadotropins (FSH) are part of the diagnostic features for Klinefelter Syndrome.
PMID:5083415	SUPPORT	Pathologic testicular findings in Klinefelter's syndrome 47,XXY vs 46,XY-47,XXY.	While this snippet doesn't provide specifics, the title suggests in-depth pathological features, likely supporting hormone-related findings.
PMID:17766718	PARTIAL	We found increased FSH/inhibin B ratio as a possible sign of Sertoli cell dysfunction. However, serum levels of T were high normal suggesting an altered pituitary-gonadal set point.	This study finds high normal testosterone in infants, which could partially support the statement but does not represent adult KS diagnosis.

notes

Low testosterone and high FSH levels indicative