Mosaicism in Turner Syndrome - GGH Journal

type-karyotype correlations in abnormal cell line be pursued in
Turner syndrome, and the fullblown
patients whose clinical findings
syndrome can be seen in suggest the clinical diagnosis of
patients mosaic with a normal Turner syndrome and yet who
cell line. Conversely, fertility appear karyotypically normal
and relatively normal stature in on initial testing of peripheral
individuals with pure 45,X have blood? Third, how should the
been reported. These occurrences
presence of mosaicism for a
may possibly represent 45,X cell line be interpreted in
mosaicism only in the affected older women, given that loss of
tissue and not in unaffected the second sex chromosome in
tissues.
tissue culture appears to be a
While mosaicism for a normal normal feature of aging?11
or isochromosome X cell line is Fourth, mosaicism for part or all
relatively common among liveborn
of the Y chromosome presents
females with Turner syn-
a unique problem in patients
drome, it is infrequently found in with Turner syndrome and is
abortuses with X chromosome responsible for one of the few
abnormalities.8 It is the 45,X reliable phenotype-karyotype
chromosome complement that correlations in the disorder:
is associated with high fetal the risk for gonadoblastoma.
mortality and that is responsible Finally, one other problem
for 10% of recognized embryonic
caused by mosaicism for sex
and fetal loss at 5 weeks of chromosome aneuploidy is its
gestational age.9 It is estimated
that less that 1 % of 45,X conceptuses
significance when it is detected
prenatally.
survive to birth.8 It Mosaicism in Turner syn-
has been suggested that all drome in which there is a 45,X
liveborn individuals with 45,X cell line and a second cell line
are mosaic to some degree for containing an X chromosome
a cell line with 2 sex chromosomes,
that is also abnormal, eg,
and that it is this occult 45,X/46,X,i(Xq) ;45,X/46,X+r(X),
mosaicism that has allowed will not be addressed here.
them to survive. A single These patients do not differ
study1O attempted to address phenotypically from 45,X
this hypothesis. In none of 10 individuals.
patients karyotyped (skin and An adequate number of cells
blood) was a normal cell line need to be evaluated to rule out
detected. Nonetheless, it is still mosaicism. Most laboratories
possible that the mosaicism will count between 25 and 50
exists in tissues other than cells to rule out mosaicism of
peripheral lymphocytes or 2% to 5% or more. Simpson?
fibroblasts, that there is hypothesized that mosaicism
mosaicism limited to the placenta
for Turner syndrome is always
that allows for survival, or detectable in blood and that
that a normal cell line is present karyotyping of fibroblasts is not
long enough in embryogenesis necessary to detect a second
to ensure that the infant is carried
abnormal cell line. Only 1 of
to term, and then is lost pri-
our 131 patients who are mosa-
or to birth.
ic for Turner syndrome is normal
The phenomenon of mosaicism
in blood and mosaic in
in Turner syndrome presents
fibroblasts. In all others, the
several problems for theclinician. mosaicism was detectable in
The first is the influence
peripheral lymphocytes. It is
of a normal 46,XX cell line probably appropriate to discard
on phenotype and prognosis, the diagnosis of Turner syndrome
ie, how hard should one search
if none of 50 lympho-
for a normal cell line? The second
cytes counted is abnormal, and
is the converse: how and fibroblast karyotyping is probacytes
when should mosaicism for an bly unnecessary unless clinical
findings for Turner syndrome
are highly suggestive of the
diagnosis.
Should one search for a
normal cell line in patients
with Turner syndrome and a
45,X karyotype?
The answer is "probably not."
The presence of a 46,XX cell
line in blood or in skin does not
accurately predict taller stature,
guarantee a better chance of
fertility, or promise fewer complications
of Turner syndrome.
Although some reviews in the
literature claim that 45,X/46,XX
patients are generally more
mildly affected,4.13 we have not
found this to be true in our
patients (Tables 1 and 2).
Although mosaics are more
likely to have spontaneous
menses, among our patients
they are no more likely to be
fertile. They are less likely to
have congenital lymphedema
and the physical features such
as nuchal webbing and nail
changes that are secondary to
lymphedema. Lymphedema is
far more common in infants with
45,X than in any other karyotype
abnormalities for Turner
syndrome. Thus, patients with
45,X are more likely to be diagnosed
at birth than are other
Turner syndrome patients,
explaining the younger mean
age of diagnosis in this group.
It is important to remember
that the only persons who will
come to medical attention for
the diagnosis of Turner syndrome
will be those who have
some clinical stigmata to suggest
the diagnosis. On the
basis of current knowledge, it is
useful, "if not necessary," to try
to find a low level of mosaicism
(less than 5%) for a normal
46,XX cell line in patients with
Turner syndrome.
How important or useful is
it to search for an abnormal
chromosome complement in
females in whom the question
of the diagnosis of Turner syndrome
is raised, but a cursory
study of the karyotype is 46,XX?
It is reasonable to assume