Sex Chromosome Abnormalities (SCA) can manifest in a variety of ways. The goal of this section is to provide information on some of the more common types of SCA and the associated syndromes that arise. Those syndromes that will be covered include Klinefelter Syndrome (KS), Turner’s Syndrome and XYY Syndrome.
KS is the most common chromosomal abnormality in humans. It occurs in 1 in 500 to 1 in 1000 live births (Pinyerd & Zipf, 2003). It is a form of aneuploidy where there is typically an extra or missing sex chromosome. Approximately 80% of the cases of KS are of the 47,XXY variant where there is an extra X chromosome rather than the typical 46. A number of variants of KS, referred to as mosaics, have also been found including: 48,XXYY, 48, XXXY, 49,XXXYY and 49,XXXXY. As the chromosomal abnormalities increase, so do the deficits experienced by the individual (Chen, 2004).
The extra X chromosome in KS results from either meiotic nonsdysjunction (a failure of the X’s or X & Y chromosomes to pair and exchange genetic material) resulting in a sperm with both an X and a Y chromosome or egg cell that has two X chromosomes. The other method through which KS can develop is when a mitotic nondysjunction occurs in the developing zygote resulting in a sperm cell with both an X and a Y chromosome or an egg with two X chromosomes combining with a normal sperm or egg cell. Each form of nondysjunction results in the 47, XXY variant of KS (Visootsak & Graham, 2001). Approximately 50% of the chromosomal transmissions leading to KS come from the father and increased maternal age appears to be associated to a slight degree with KS.
Physically, males with KS are difficult to distinguish from XY males due to the variability in physical features present in the syndrome and the fact that there is no obvious facial dysmorphology. The most common physical abnormality that exists for males with KS is small testicular size due to a failure of the testes to grow. Individuals with KS can have gynecomastia (enlargement of the breast tissue) which ranges in frequency from 10% to 88% depending on the study. Decreased facial and body hair is also a common finding. Head circumference tends to remain around the 50th percentile while height approximates the 75th percentile. The increase in height is usually a function of increased leg length, but it should also be noted that the arms of males with KS tend to be longer, making the person appear to be lanky and often uncoordinated. The shoulders are narrower and hips wider than in the non-KS male.
In the cognitive domain language-based developmental delays have been some of the most common findings in individuals with KS. Individuals with KS are prone to a disproportionate level of Reading Disorders (see the section on Learning Disorders for a complete description); however, the findings seem to suggest that language development in general is affected in boys with the 47,XXY karyotype. For example, research has shown with some consistency that children and adolescents with KS are more likely to have verbal IQ scores that are lower than performance IQ scores. In addition, the verbal IQ scores of boys with KS are typically below that of non-affected boys, but remain in the average range. Interestingly, it appears that the opposite trend is found in adult males with KS, with verbal scores increasing relative to and often exceeding non-verbal scores. There have also been some studies that have not found any differences between verbal and non-verbal abilities in KS or between individuals with KS and those who are unaffected. It is also important to note that the presence of language-based learning disorders (i.e., Reading Disorder & Disorder of Written Expression) is more likely when verbal abilities are lower than performance while non-verbal learning disorders are more common when performance IQ is lower than verbal IQ. Research on adults with KS has shown that they are more likely to have deficits with the speed and efficiency with which verbal information is processed and also tend to have greater difficulty on tasks that require verbal executive functions.[Use this link to see a live presentation on the learning and emotional issues in KS.]
XYY Syndrome occurs in approximately 1 in 1,000 live male births. There are typically no physical abnormalities, but these males (like those with KS) tend to be taller than average, falling in the 75th percentile in terms of height. Their upper and lower extremities tend to be longer than average (accounting for most of the height increase). As a result, XYY males often appear lanky, awkward and uncoodrinated. During puberty XYY adolescents are likely to experience severe acne that requires dermatological care. Although numerous cases of infertility have been reported, most men with XYY do not have problems in this domain.
XYY males are generally of average intellectual functioning, but often lower than their non-XYY counterparts. Like KS males, those with XYY are prone to language-based learning problems, including Reading Disorder (Dyslexia). They also have problems with motor coordination, which makes their ability to participate in sports more difficult. While XYY males are not thought to be at higher risk for psychological disorders, problems with self-esteem due to learning and motor issues are common. Behaviorally, problems with hyperactivity and behavior tantrums are more common than in non-XYY males. As adults, XYY males may be more impulsive and emotionally immature.
The most common type of TS is the 45,XO variant; however, females with the syndrome can have part of one or both X chromosomes missing or can have a 46,XX variation. The disorder occurs in 1 in 2,000 live births and is reportedly the cause of 15% of spontaneous abortions. Females with TS are typically of short stature and prone to ovarian failure (both occur in approximately 95% of females with TS). Intelligence is typically average, but individuals with TS are more likely to demonstrate visuospatial deficits including poor handwriting and likely underdeveloped arithmetic skills (Pennington et al., 2001). There is a greater likelihood of otitis media (OM; ear infections) in TS females and when the OM occurs with high frequency early during development, research has found an association with language-based disorders such as Reading Disorder.
Women and girls with 47, XXX Syndrome demonstrate more global delays that cut across a variety of cognitive domains; however, mental retardation is uncommon. The females in this group are also more likely to experience deficits in problem solving and reasoning abilities (Bender, Linden & Harmon, 2001).
Given the likelihood of verbal and non-verbal learning problems as well as behavioral and emotional issues that are associated with the various SCA syndromes, the purpose of the neuropsychological evaluation is to determine what if any areas of deficit exist and if there are learning and emotional problems, the types of interventions and services that will be necessary for remediation.
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