Porth's Essentials of Pathophysiology, 4e

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Genetic and Congenital Disorders

C h a p t e r 6

syndrome, with abnormalities ranging from essentially none to webbing of the neck with redundant skin folds, nonpitting lymphedema of the hands and feet, and congenital heart defects, particularly coarctation of the aorta and bicuspid aortic valve. There also may be abnormalities in kidney development (i.e., abnormal location, abnormal vascular supply, or double collect- ing system). There may be other abnormalities, such as changes in nail growth, high-arched palate, short fourth metacarpal, and strabismus. Although most women with Turner syndrome have normal intelligence, they may have problems with visuospatial organization (e.g., difficulty in driving, nonverbal problem-solving tasks such as mathematics, and psychomotor skills) and may have attention deficit disorder. The diagnosis of Turner syndrome often is delayed until late childhood or early adolescence in girls who do not present with the classic features of the syndrome. Early diagnosis is an important aspect of treatment for Turner syndrome. It allows for counseling about the phenotypic characteristics of the disorder; screening for cardiac, renal, thyroid, and other abnormalities; and provision of emotional support for the girl and her family. Because of the potential for delay in diagnosis, it has been recommended that girls with unexplained short stature (height below the fifth percentile), webbed neck, peripheral lymphedema, coarctation of the aorta, or delayed puberty have chromosome studies done. 40 The management of Turner syndrome begins during childhood and requires ongoing assessment and treat- ment. Growth hormone therapy is now standard treat- ment and can result in a gain of 6 to 10 cm in final height. Estrogen therapy, which is instituted around the normal age of puberty, is used to promote development and maintenance of secondary sexual characteristics. 34–36 There are also health concerns for adult women with Turner syndrome. 34–42 Until recently, females with Turner syndrome received intensive medical care dur- ing childhood but were discharged from specialty clin- ics after induction of puberty and attainment of final height. It is now known that women with Turner disease have increased morbidity due to cardiovascular disease and gastrointestinal, renal, and endocrine disorders. Adults with Turner syndrome continue to have reduced bone mass, and this has been associated with increased risk of fractures. Klinefelter Syndrome Klinefelter syndrome is a condition of testicular dys- genesis accompanied by the presence of one or more extra X chromosomes in excess of the normal male XY complement. 2,43–47 Most males with Klinefelter syn- drome have one extra X chromosome (47,XXY). In rare cases, there may be more than one extra X chromosome (48,XXXY). The presence of the extra X chromosome in the 47,XXY male results from nondisjunction during meiotic division in one of the parents. Klinefelter syndrome is characterized by enlarged breasts, sparse facial and body hair, small testes, and the inability to produce sperm (Fig. 6-12). 45–47 Regardless

Tall stature

Lack of facial hair

Narrow shoulders

Gynecomastia

Long arms and legs

Wide hips

Decreased pubic hair

Testicular atrophy Infertility

Barr body

XXY

FIGURE 6-12. Clinical features of Klinefelter syndrome.

of the number of X chromosomes present, the male phenotype is retained. The condition often goes unde- tected at birth. The infant usually has normal male genitalia, with a small penis and small, firm testicles. At puberty, the intrinsically abnormal testes do not respond to stimulation from the gonadotropins and undergo degeneration. Low testosterone levels lead to tall stature with abnormal body proportions in which the lower part of the body is longer than the upper part. Later in life, the body build may become heavy, with a female distribution of subcutaneous fat and variable degrees of breast enlargement. There may be deficient secondary male sex characteristics, such as a voice that remains feminine in pitch and sparse beard and pubic hair. While the intellect usually is normal, most 47,XXY males have some degree of language impairment. They often learn to talk later than do other children and often have trouble with learning to read and write.