Page 254 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

240 C H A P T E R 6 Genetic and Pediatric Diseases Low posterior hairline Short stature
Webbing of neck Coarctation of
normal males), extragonadal germ cell tumors, and auto- Broad chest aorta
immune diseases such as systemic lupus erythematosus. Cubitus valgus
and widely Streak ovaries,
Turner Syndrome spaced nipples infertility,
amenorrhea
Turner syndrome, characterized by primary hypogonad- Pigmented nevi
ism in phenotypic females, results from partial or complete
monosomy of the short arm of the X chromosome. With Peripheral
routine cytogenetic methods, the entire X chromosome is lymphedema
found to be missing in 57% of patients, resulting in a 45,X at birth
karyotype. These patients are the most severely affected,
and the diagnosis often can be made at birth or early in TURNER SYNDROME
childhood. Typical clinical features associated with 45,X
Turner syndrome include significant growth retardation, Incidence: 1 in 3000 female births
leading to abnormally short stature (below the third per- Karyotypes:
centile); swelling of the nape of the neck due to distended Classic: 45,X
lymphatic channels (in infancy) that is seen as webbing of Defective
the neck in older children; low posterior hairline; cubitus second X
valgus (an increase in the carrying angle of the arms); chromosome: 46,X,i(Xq)
shieldlike chest with widely spaced nipples; high-arched 46,XXq–
palate; lymphedema of the hands and feet; and a variety of 46,XXp–
congenital malformations such as horseshoe kidney, bicus- 46,X, r(X)
pid aortic valve, and coarctation of the aorta (Fig. 6–16). Mosaic type: 45,X/46,XX
Cardiovascular abnormalities are the most common cause
of death in childhood. In adolescence, affected girls fail to Figure 6–16 Clinical features and karyotypes of Turner syndrome.
develop normal secondary sex characteristics; the genitalia
remain infantile, breast development is minimal, and little accelerated loss of oocytes, which is complete by age
pubic hair appears. Most patients have primary amenor- 2 years. In a sense, therefore, “menopause occurs before
rhea, and morphologic examination reveals transformation menarche,” and the ovaries are reduced to atrophic fibrous
of the ovaries into white streaks of fibrous stroma devoid strands, devoid of ova and follicles (streak ovaries). Because
of follicles. The mental status of these patients usually is patients with Turner syndrome also have other (nongo-
normal, but subtle defects in nonverbal, visual-spatial nadal) abnormalities, it follows that some genes for normal
information processing have been noted. Curiously, hypo- growth and development of somatic tissues also must
thyroidism caused by autoantibodies occurs, especially in reside on the X chromosome. Among the genes involved
women with isochromosome Xp. As many as 50% of these in the Turner phenotype is the short stature homeobox
patients develop clinical hypothyroidism. In adult patients, (SHOX) gene at Xp22.33. This is one of the genes that remain
a combination of short stature and primary amenorrhea should active in both X chromosomes and is unique in having an
prompt strong suspicion for Turner syndrome. The diagnosis active homologue on the short arm of the Y chromosome.
is established by karyotyping. Thus, both normal males and females have two copies of
this gene. One copy of SHOX gives rise to short stature.
Approximately 43% of patients with Turner syndrome Indeed, deletions of the SHOX gene are noted in 2% to 5%
either are mosaics (one of the cell lines being 45,X) or have of otherwise normal children with short stature. Whereas
structural abnormalities of the X chromosome. The most one copy of SHOX can explain growth deficit in Turner
common is deletion of the short arm, resulting in the for- syndrome, it cannot explain other important clinical
mation of an isochromosome of the long arm, 46,X,i(X)
(q10). The net effect of the associated structural abnormali-
ties is to produce partial monosomy of the X chromosome.
Combinations of deletions and mosaicism are reported. It
is important to appreciate the karyotypic heterogeneity
associated with Turner syndrome because it is responsible
for significant variations in the phenotype. In contrast with
the patients with monosomy X, those who are mosaics or have
deletion variants may have an almost normal appearance and
may present only with primary amenorrhea.

The molecular pathogenesis of Turner syndrome is not
completely understood, but studies have begun to shed
some light. As mentioned earlier, both X chromosomes are
active during oogenesis and are essential for normal devel-
opment of the ovaries. During normal fetal development,
ovaries contain as many as 7 million oocytes. The oocytes
gradually disappear so that by menarche their numbers
have dwindled to a mere 400,000, and when menopause
occurs fewer than 10,000 remain. In Turner syndrome,
fetal ovaries develop normally early in embryogenesis, but
the absence of the second X chromosome leads to an