Which of the following is most likely characteristic of persons with Klinefelter syndrome?
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HistoryHypogonadism, gynecomastia, and infertility are common symptoms that lead to the diagnostic evaluation of males for Klinefelter syndrome. Other symptoms include the following:
PhysicalFrequently associated medical disordersThese include the following. [18] Motor, cognitive, and behavioral dysfunction Poor muscle tone and strength, as well as impaired gross and fine motor skills, coordination, dexterity, and running ability, are observed. Synkinetic movements and tremor can be seen in early childhood and may persist into adulthood. [19, 20] Cognitive phenotype is manifested as deficits in the specific domains of language and executive functions. Expressive language is affected more than comprehension or receptive language skills. Problems in understanding complex grammatical constructions, oral language production, word retrieval, and oral narrative construction are observed in these patients. [21] A study by Skakkebæk et al suggested that in persons with KS, the level of social engagement has an impact on executive cognitive functioning and/or vice versa. The study indicated that while lower general intelligence seems to be the principal factor in memory deficits among these individuals, a combination of decreased intelligence and lower social skills produce deficits in executive function. [22] Schizophrenia, psychosis, and bipolar disorder have been reported in males with Klinefelter syndrome. [23] Tumors/Cancer Mediastinal tumors may occur in young patients, presenting as precocious puberty; histologically, these neoplasms are classified as mixed germ cell tumors. Mediastinal tumors in older males present with thorax-associated symptoms, primarily chest pain, dyspnea, and cough; mixed germ cell tumors are more common, but teratomas and other mixed tumors occur. [24] Breast cancer and testicular cancer are reported, although a clear relationship between Klinefelter syndrome and testicular cancer has not been documented. Vascular disease Vascular diseases associated with Klinefelter syndrome include hypostatic ulceration, deep vein thrombosis, pulmonary embolism, and ischemic heart disease. Endocrine/metabolic and autoimmune diseases Hypogonadism (pathognomonic) and associated osteoporosis occur. Bone density decreases in 25% of males with Klinefelter syndrome, with this most likely being related to decreased bone formation, increased bone resorption, and/or hypogonadism. An increased incidence of diabetes mellitus, obesity, hypothyroidism, Sjögren syndrome, rheumatoid arthritis, and systemic lupus erythematosus have been reported in males with Klinefelter syndrome. Other observationsGrowth Infants and children achieve normal height, weight, and head circumference. Height velocity shows a notable increase between ages 5 and 8 years. Adults with Klinefelter syndrome are usually taller than nonaffected adult males, reaching a mean final height of about 185 cm (73 in). XXY males (see the image below) also have disproportionately long arms and legs. About 25% of patients have fifth-finger clinodactyly. Some males with Klinefelter syndrome variant 49,XXXXY have short stature. G-banded 47,XXY karyotype.CNS Contrary to other genetic syndromes that arise from chromosomal trisomy (eg, Down syndrome, trisomy 18), the overall cognitive abilities of males with Klinefelter syndrome typically are within the range of average intellectual ability. [25] Most males with the 47,XXY karyotype have normal intelligence. Intellectual disability occurs in males with Klinefelter syndrome variants, who have a higher number of X chromosomes. About 70% of patients have minor developmental and learning disabilities. These may include academic difficulties, delayed speech and language acquisition, diminished short-term memory, decreased data-retrieval skills, reading difficulties, dyslexia, and attention deficit disorder. Evidence for more general impairments in language has been consistent, with the most widely observed deficits having been reported in encoding of verbal information, auditory processing, comprehension, and processing speed. Expressive speech and verbal fluency are also affected. [26] Behavioral problems and psychological distress are reported and may be due to poor self-esteem, compromised psychosocial development, or an inability to deal with stress. Psychiatric disorders with features of anxiety, depression, neurosis, and psychosis are more common than in the general population. Dental About 40% of patients have taurodontism, a dental finding characterized by enlargement of the molar teeth by an extension of the pulp. In comparison, the incidence of taurodontism is about 1% in XY males. Sexual characteristics Genital abnormalities are not commonly observed in 47,XXY males. This is an important observation because Klinefelter syndrome is considered a cause of genital abnormality or ambiguity. [27] The genital phenotype can include complete sex reversal, true hermaphroditism (eg, ovotestes), testicular feminization, and ambiguous genitalia/undervirilization (eg, hypospadias, micropenis, epispadias, female external genitalia). Pubertal changes with lack of secondary sexual characteristics are due to decreased androgen production. This results in sparse facial, body, or sexual hair; a high-pitched voice; and body fat distribution as is observed in females. By late puberty, 30-50% of boys with Klinefelter syndrome present with gynecomastia, which is due to elevated estradiol levels and an increased estradiol:testosterone ratio. The risk of developing breast carcinoma in Klinefelter syndrome is at least 20 times higher than in healthy individuals. There is also an increased risk of extragonadal germ cell tumors such as embryonal carcinoma, teratoma, and primary mediastinal germ cell tumor. Postpubertal males may have testicular dysgenesis (small firm testis; testis size < 10 mL). Infertility, azoospermia, or both may result from atrophy of the seminiferous tubules. Most males with a 47,XXY karyotype are infertile, but patients with Klinefelter syndrome mosaicism (46,XY/47,XXY) can be fertile. Guidelines for the assessment and treatment of people with fertility problems have been established. [28] A literature review by Deebel et al indicated that, while azoospermia is a characteristic of Klinefelter syndrome, patients are frequently positive for spermatogonia. Indeed, spermatogonial cells were found in 100% of fetal/infantile patients and in 83%, 42.7%, and 48.5% of prepubertal, peripubertal, and adult patients. In addition, positive spermatogonia results were found in 46.4% of peripubertal/adolescent patients and 24.3% of adult patients, who were negative for spermatozoa. [29] Cardiac and circulatory problems [30] Mitral valve prolapse occurs in 55% of patients. Varicose veins occur in 20-40% of patients. The prevalence of venous ulcers is 10-20 times higher than in healthy individuals, and the risk of deep vein thrombosis and pulmonary embolism is increased. A Swedish study found the standardized incidence ratio for venous thromboembolism (VTE) in Klinefelter syndrome to be 6.43, with a ratio of 12.10 in persons younger than age 30 years and 2.07 in persons aged 70 years or older. Based on the study's findings, an association exists between Klinefelter syndrome and a high risk for VTE. The authors suggest that Klinefelter syndrome could be recognized as a genetic hypercoagulable state. [31] A study by Chang et al also found the thrombosis risk to be higher in Klinefelter syndrome, with hazard ratios for VTE and total thrombotic death, as measured against a comparison cohort, being 3.95 and 1.76, respectively. The investigators also reported an insignificant decrease in venous thromboembolism and thrombotic deaths in patients who received testosterone treatment. [32] Klinefelter syndrome variants/sex chromosome aneuploidies Variants of Klinefelter syndrome are as follows [33] [34] :
CausesIn 1959, Klinefelter syndrome was found to be caused by a supernumerary X chromosome in a male. [35] The 47,XXY karyotype of Klinefelter syndrome spontaneously arises when paired X chromosomes fail to separate (nondisjunction in stage I or II of meiosis, during oogenesis or spermatogenesis). [36] Maternal and paternal meiotic nondisjunction each account for approximately 50% of Klinefelter syndrome cases. Seventy-five percent of maternal nondisjunction cases are caused by meiosis I errors, which are associated with increased maternal age. Increased paternal age has been linked to a possible increased risk of Klinefelter syndrome. [37] Postfertilization nondisjunction is responsible for mosaicism, which is seen in approximately 10% of Klinefelter syndrome patients. Men with mosaicism are less affected and are often not diagnosed. [6] The androgen receptor (AR) gene encodes the androgen receptor, which is located on the X chromosome.
The most common karyotype is 47,XXY, which accounts for 80-90% of all cases. Mosaicism (46,XY/47,XXY) is observed in about 10% of cases. Other variant karyotypes, including 48,XXYY; 48,XXXY; 49,XXXYY; and 49,XXXXY, are rare.
Author Germaine L Defendi, MD, MS, FAAP Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: American Academy of Pediatrics Disclosure: Nothing to disclose. Specialty Editor Board Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Nothing to disclose. Chief Editor Luis O Rohena, MD, PhD, FAAP, FACMG Deputy Chief, Department of Pediatrics, Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio Luis O Rohena, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics Disclosure: Nothing to disclose. Additional Contributors Harold Chen, MD, MS, FAAP, FACMG Professor, Department of Pediatrics, Louisiana State University Medical Center Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics Disclosure: Nothing to disclose. Which of the following is most likely a characteristic of a person with Klinefelter syndrome quizlet?Which of the following is most likely a characteristic of persons with Klinefelter syndrome? They have undeveloped testes.
Which of the following describes Klinefelter syndrome quizlet?Which of the following is true regarding Klinefelter syndrome? A chromosomal disorder in which males have an extra X chromosome, making them XXY instead of XY.
Which of the following is most likely a function performed by a childs peer group that would be difficult?Which of the following is most likely a function that a child's peer group performs which is difficult for a sibling to do? it helps a child master anxieties and conflicts.
What is a characteristic of reciprocal socialization?Reciprocal socialization "is a socialization process that is bidirectional; children socialize parents just as parents socialize children". For example, the interaction of mothers and their infants is sometimes symbolized as a dance or dialogue in which following actions of the partners are closely coordinated.
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