Klinefelter Syndrome
Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh in Male Infertility in Reproductive Medicine, 2019
Seventy-eight comorbidities have been associated with KS [16] reducing the average life span by 2.1 years [17]. These include risk factors associated with cardiovascular disease such as higher risk of thrombosis (DVT and pulmonary embolism), insulin resistance, obesity, metabolic syndrome and diabetes; increased risk of certain infectious diseases, malignancy such as breast cancer, lymphoma, extragonadal germ-cell tumors, autoimmune diseases, such as systemic lupus erythematous (SLE), rheumatoid arthritis, epilepsy, tooth decay, and osteoporosis [17,18]. The reduction in life expectancy also seems to be indiscriminate of the karyotype with no significant difference being identified between the most common type (47,XXY) and the less common types (karyotypes with more than one additional X chromosomes and mosaicism) [19].
Chromosome abnormalities
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Information on the long-term outlook for individuals with sex chromosome abnormalities is now available from studies of infants detected at birth by population studies. In general the phenotypic effects in XXY, XYY and 45,X individuals are mild; in particular, serious mental retardation is exceptional, although there is a slight reduction in mean intelligence quotient (IQ), along with an increased incidence of learning disability, often correctable with support. This may be more marked in XXX individuals. It is important that parents of a newly diagnosed child, as well as couples in whom such a condition has been detected by amniocentesis, are given an accurate picture of the likely situation, rather than one biased by the more serious problems of the minority attending hospital clinics.
Sex Chromosome Anomalies
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Jacobs et al. (94) studied nondisjunction in males with 47,XXY karyotypes. Fifty-three percent were attributable to paternal MI errors, 34% to maternal MI errors, and 9% to maternal Mil errors. Three percent were due to PZM events. In the majority of maternal errors, there was clear evidence of recombination involving the nondisjoined chromosomes, suggesting that failure to recombine is not a major factor in nondisjunction of the X chromosomes in female meiosis. Maternal age was significantly increased among the maternally derived XXY cases, associated primarily with those with MI errors. Paternal age was not increased in paternally derived cases. Thomas et al. (95) investigated the nondisjunctional event in paternally derived 47,XXY males using polymorphisms within PARI. Among informative results, 16% showed single crossovers, 2% had a double crossover, and 83% had no evidence of a crossover. Thus, most XXY males of paternal origin result from a meiosis in which the X and Y chromosomes fail to recombine. There was no association with recombination frequencies in the smaller PAR2 region, or with the presence of microdeletions within PARI.
A case of Aicardi syndrome associated with duplication event of Xp22 including SHOX
Published in Ophthalmic Genetics, 2023
Leyla Yavuz Saricay, Sandra Hoyek, Ayush Ashit Parikh, Grace Baldwin, Olaf a Bodamer, Efren Gonzalez, Nimesh A. Patel
Aicardi syndrome (AIS) is a well-characterized neurodevelopmental disorder that primarily affects females and was described in 1965 by Dr Jean Aicardi as a triad of partial or complete agenesis of the corpus callosum, infantile spasms, and pathognomonic chorioretinal lacunae (1). Since this initial description, other neurological and ophthalmic features have been observed, including cortical polymicrogyria and heterotopia, developmental delay, microphthalmia, and optic nerve coloboma or atrophy (2–4). Given the overwhelming predominance of AIS in females or 47, XXY males and evidence showing excessive skewing of X-inactivation in affected patients, AIS has been classified as an X-linked dominant disorder that is lethal in hemizygous males (5,6). Previous studies have sought to characterize the genetic basis of AIS further and have suggested chromosomal aberrations at the Xp22 locus. However, to our knowledge, there has been no identification of a specific gene variant in this chromosomal region or at any other genetic locus (5–8). Therefore, specific diagnostic genetic testing is unavailable for AIS, and the diagnosis is largely clinical (9).
To Disclose or Not to Disclose: Secondary Findings of XXY Chromosomes
Published in The American Journal of Bioethics, 2022
Benjamin S. Wilfond, Devan M. Duenas, Liza-Marie Johnson
Mr. Robinson was 25 years old when he enrolled in a study to investigate the role of the environment and the microbiome in the phenotypic expression of sickle cell disease. His participation consisted of a single visit during which he provided blood and saliva samples. The informed consent form stated that if incidental clinical findings were discovered, they might be disclosed if “urgently important to a participant’s health.” Genomic sequencing of his samples performed two years later in a non-CLIA research laboratory indicated the presence of XXY chromosomes, also known as Klinefelter’s syndrome. The research team does not know if Mr. Robinson has previously received a diagnosis of Klinefelter’s syndrome. He continues to be followed in the hematology clinic for his sickle cell disease.
Noninvasive prenatal screening in southeast China: clinical application and accuracy evaluation
Published in Expert Review of Molecular Diagnostics, 2022
Li Wen, Jiye Gao, Leilei Huang, Dongmei Li, Guansheng Zhong
Though there was no significant association between Z-score of NIPS suggested positive cases and true positive results in SCA using logistic regression analysis, ROC curve analysis showed the relatively satisfied AUC for SCA separately (Table 5). The optimal cutoff values were −4.858, 36.527, 23.669 and 70.346 for 45,X, 47,XXX, 47,XXY, and 47,XYY, respectively. Moreover, the sensitivity was high (45,X: 84.21%; 47,XXX: 100%; 47,XXY: 93.18%; 47,XYY: 100%) while the specificity was low (45,X: 48.15%; 47,XXX: 85.71%; 47,XXY: 40.00%; 47,XYY: 60.00%). According to the optimal cutoff of Z-score, NIPS-positive cases of SCA were divided into three groups: the intermediate risk group (3 ≤ Z-score < cutoff or cutoff < Z-score < −3), the high-risk group (Z score ≥ cutoff or Z score ≤ cutoff) and all risk group (Z-score ≥ 3). As shown in Table 5, significant differences of PPV between intermediate risk group and high-risk group were expressed in 45,X, 47,XXX, and 47,XYY. Nevertheless, no difference was found in 47,XXY between groups. Surprisingly, there seemed to be a higher PPV along with the higher Z-score except for 47,XXX.
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