47,XXY-Klinefelter Syndrome. his is the most common sex chromosome abnormality and found in approximately 1 in 600 male infants. he additional X chromosome is maternally or paternally derived with equal propensity Qacobs, 1995; Lowe, 2001). The association with either advanced maternal or paternal age is weak (Milunsky, 2004).
Like 47,XX, newborns with 47,Y usually appear phenotypically normal and do not have a higher incidence of anomalies. As children, boys are typically taller than average and have normal prepubertal development. However, they have gonadal dysgenesis, do not undergo normal virilization, and require testosterone supplementation beginning in adolescence. They may develop gynecomastia. IQ scores usually lie in the average to low-average range, and many have delays in language development and reading (Boada, 2009; Girardin, 2011).
47,XY. This aneuploidy occurs in approximately 1 in 1000 male newborns. As with 47,XXand Y individuals, afected boys tend to be tall. A third have macrocephaly, nearly two thirds demonstrate hypotonia, and tremors are also common (Bardsley, 2013). Rates of major anomalies are not elevated, although hypertelorism and clinodactyly may be identified in more than hal. Pubertal development is normal, and fertility is unimpaired. ffected children carry risks for oral and written language impairments, attention deicit disorder is diagnosed in more than half, and the rate of autism spectrum disorder is also increased (Bardsley, 2013; Ross, 2009). Intelligence scores generally lie in the normal range.
Males with more than two Y chromosomes-48Yor with both additional X and Y chromosomes-48,YYor 49,XYY-are more likely to have congenital abnormalities, medical problems, and intellectual disability (Tartaglia, 2011).
• Abnormalities of Chromosome Structure
Structural chromosomal abnormalities include deletions, duplications, translocations, isochromosomes, inversions, ring chromosomes, and mosaicism (see Table 13-1). heir overall birth prevalence approximates 0.3 percent (Nussbaum, 2007). Identiication of a structural chromosomal abnormality raises two primary questions. First, what phenotypic abnormalities or later developmental abnormalities are associated with this finding? Second, is evaluation of parental karyotype indicated-speciically, are the parents at increased risk of carrying this abnormality? If so, what is their risk of having future afected ofspring?
A chromosomal deletion indicates that a portion of a chromosome is missing, whereas a duplication means that a portion has been included twice. Most deletions and duplications occur during meiosis and result from malalignment or mismatching during the pairing of homologous chromosomes. he misaligned segment may then be deleted, or if the mismatch remains when the two chromosomes recombine, it may result in a deletion in one chromosome and duplication in the other (Fig. 13-6). When a deletion or duplication is identified in a fetus or infant, parental karyotyping should be ofered, because if either parent carries a balanced translocation, the recurrence risk in subsequent pregnancies is signiicantly increased. Deletions involving DNA segments large enough to be seen with standard cytogenetic karyotyping are identiied in approximately 1 in 7000 births (Nussbaum, 2007). Common
FIGURE 13-6 A mismatch during pairing of homologous chromosomes may lead to a deletion in one chromosome and a duplication in the other. Del = deletion; Dupl duplication.
deletions may be referred to by eponyms-for example, del 5p is called cri du chat syndrome.