Forms of Gonadal Failure Turner Syndrome The diagnosis of Turner syndrome requires the presence of characteristic features in phenotypic females coupled with complete or partial absence of the second sex chromosome, with or without cell line mosaicism. Most affected individuals have a 45,X karyotype, while others have mosaic karyotypes (i.e., 45,X/46,XX; 45,X/46,XY). Intrauterine growth restriction is common in infants with a 45,X karyotype. After birth, these patients generally grow slowly, beginning in the second or third year of life. They typically have many of the associated stigmata, including lymphedema and sometimes large cystic hygromas of the neck at birth; a webbed neck; multiple pigmented nevi; disorders of the heart, kidneys (most commonly horseshoe), and great vessels (most commonly coarctation of the aorta); and small hyperconvex fingernails (35) (Fig. 29.10). Diabetes mellitus, thyroid disorders, essential hypertension, and other autoimmune disorders are often present in individuals with 45,X karyotypes.
Most 45,X patients have normal intelligence, but many affected individuals have an unusual cognitive defect characterized by an inability to appreciate the shapes and relations of objects with respect to one another (i.e., space-form blindness). Patients with a small ring X chromosome have an increased risk of mental retardation (36). As they grow older, affected children typically are shorter than normal. Although they do not develop breasts at puberty, some pubic or axillary hair may develop because appropriate adrenarche can occur with failure of thelarche (i.e., breast development).
Figure 29.10 Typical appearance of two individuals with 45,X gonadal dysgenesis. A: This 16-year-old individual has obvious short stature, a webbed neck, shortened fourth metatarsals, and a thoracotomy scar from the repair of the coarctation of the aorta that was performed at 13 years of age. B: This 11-year-old individual also has obvious short stature and stigmata of Turner syndrome. Note that these two individuals look more like each other than they might look like any genetic siblings.
Although less severe short stature and some adolescent development may occur with chromosomal mosaicism, it is reasonable to assume that any short, slowly growing, sexually infantile girl has Turner syndrome until proved otherwise because this disorder is so prevalent (about 1 in 2,500 newborn phenotypic females). In fact, the 45,X karyotype is the single most frequent chromosomal disorder in humans, but most affected fetuses are aborted spontaneously early in pregnancy. However, trisomy is the most common chromosomal type or category of abnormality in first-trimester losses.
The short stature commonly associated with the Turner phenotype appears to result from the loss of a homeobox-containing gene (which encodes for an osteogenic gene) located on the pseudoautosomal region (PAR 1) of the short arms of the X (Xp22) and Y (Yp11.3) chromosomes (37). This gene, which is called either SHOX (short stature homeobox-containing gene) or PHOG (pseudoautosomal homeobox osteogenic gene), escapes X inactivation because of its pseudoautosomal location. The gene appears to account for about two-thirds of the height deficit commonly associated with Turner syndrome.