Klinefelter syndrome: more than hypogonadism

Kanakis, George; Nieschlag, Eberhard

doi:10.1016/j.metabol.2017.09.017

Cited by 120 publications

(110 citation statements)

References 116 publications

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“…To the best of our knowledge, this is the first study to report a significant association between HH, delayed puberty and NDD morbidity using a population‐based design. Our results expand the current literature indicating neurodevelopmental problems in syndromes with hypogonadism as a clinical feature, such as Klinefelter and CHARGE syndromes …”

Section: Discussionsupporting

confidence: 89%

“…Our earlier study has demonstrated an increased risk for NDDs in Klinefelter syndrome, which has hypogonadism as one of the clinical features . NDDs and hypogonadism also co‐occur in other defined genetic syndromes such as Turner, Prader‐Willi, Bardet‐Biedl and CHARGE syndromes .…”

Section: Introductionmentioning

confidence: 96%

“…[18][19][20][21] Our earlier study has demonstrated an increased risk for NDDs in Klinefelter syndrome, which has hypogonadism as one of the clinical features. 22,23 NDDs and hypogonadism also co-occur in other defined genetic syndromes such as Turner, Prader-Willi, Bardet-Biedl and CHARGE syndromes. [24][25][26][27] Additionally, hypospadias, a common congenital malformation, which is sometimes caused by androgen insufficiency, increase the risk of an NDD.…”

mentioning

confidence: 99%

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Hypogonadotrophic hypogonadism, delayed puberty and risk for neurodevelopmental disorders

Gotby

Söder

Frisén

et al. 2019

J Neuroendocrinology

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Hypogonadotrophic hypogonadism (HH) is a rare disorder that manifests absent puberty and infertility. Genetic syndromes with hypogonadism, such as Klinefelter syndrome, are associated with an increased risk of neurodevelopmental disorders (NDDs). However, it is not clear whether patients with HH or transient delayed puberty in general, have an increased risk of NDDs. We performed a register‐based study on a national cohort of 264 patients with HH and 7447 patients diagnosed with delayed puberty that was matched with 2640 and 74 470 controls, respectively. The outcome was defined as having any of the following NDD diagnoses: (i) autism spectrum disorder (ASD); (ii) attention deficit hyperactivity disorder (ADHD); or (iii) intellectual disability (ID). Additional sensitivity analyses were performed to control for different parental and birth variables, as well as diagnosed malformation syndromes and chromosomal anomalies (ie, Down’s and Turner syndromes). Patients with HH had increased risk for being diagnosed with ASD (odds ratio [OR] = 5.7; 95% confidence interval [CI] = 2.6‐12.6), ADHD (OR = 3.0; 95% CI = 1.8‐5.1) and ID (OR = 18.0; 95% CI = 8.9‐36.3) compared to controls. Patients with delayed puberty also had a significantly increased risk of being diagnosed with an NDD. These associations remained significant after adjustments. This is the first study to demonstrate a significant association between HH, delayed puberty and NDDs in a population‐based cohort. Clinicians should be aware of the overlap between these disorders. Further studies should explore the mechanisms behind these associations.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 96%

mentioning

confidence: 99%

See 1 more Smart Citation

Hypogonadotrophic hypogonadism, delayed puberty and risk for neurodevelopmental disorders

Gotby

Söder

Frisén

et al. 2019

J Neuroendocrinology

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“…Notably, our KS patients were relatively old (all except one were above 30 years). Since KS is associated with several comorbidities such as metabolic syndrome, diabetes type 2, osteoporosis, cardiovascular diseases, thromboembolism and in young boys with language and learning difficulties and other neuropsychological problems (Kanakis & Nieschlag, ), the question arises why these patients were diagnosed so late in life. Earlier diagnosis and preventive measures such as testosterone substitution could ameliorate some of these comorbidities, thus improving the general health of the patients.…”

Section: Discussionmentioning

confidence: 99%

Genetic investigations on causes of male infertility in Western Saudi Arabia

et al. 2019

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In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y‐chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y‐chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y‐chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many‐fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.

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“…Рост увеличивается преимущественно за счет длины ног, которая при СК в среднем на 5,7 см превышает аналогичный показатель у детей контрольной группы [23]. Пропорции тела при СК несколько отличаются от характерных для других видов гипогонадизма, поскольку размах рук в большинстве случаев не превышает длины тела [24]. Увеличение грудных желез определяется примерно у трети взрослых мужчин с СК [23]; оно начиная обращать на себя внимание, как правило, в пубертатном периоде.…”

Section: клинико-лабораторные признаки ск в периоде пубертатаunclassified

Klinefelter syndrome in children and adolescents

Bespalyuk

Алексеевна²,

Чугунов

et al. 2018

Probl Endokrinol (Mosk)

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Klinefelter syndrome is a chromosomal pathology, which is the most common anomaly of sex chromosomes and the most common form of primary male hypogonadism. The presence of an extra X-chromosome in the karyotype causes infertility, azoospermia, small size of testicles, high level of gonadotropins and low level of testosterone, tallness and disproportionate physique, learning difficulties, and developmental speech disorders. Despite the high incidence of the syndrome in the population, only 25% of patients are aware of their disease during their lifetime. Late diagnosis and delayed treatment are often due to pronounced clinical polymorphism of the disease, different symptom onset time, as well as high incidence of associated conditions, so that these patients are followed by various specialists, but they are not aware of the main diagnosis. This review presents data on the history, etiology of the syndrome, clinical and laboratory features characteristic of children, adolescents, and adults. The most common associated diseases are listed and current data on their prevalence and the effect of testosterone replacement therapy on these conditions are provided.

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Klinefelter syndrome: more than hypogonadism

Cited by 120 publications

References 116 publications

Hypogonadotrophic hypogonadism, delayed puberty and risk for neurodevelopmental disorders

Hypogonadotrophic hypogonadism, delayed puberty and risk for neurodevelopmental disorders

Genetic investigations on causes of male infertility in Western Saudi Arabia

Klinefelter syndrome in children and adolescents

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