The Principles of Clinical Cytogenetics - Extra Materials - Springer

214 Cynthia Powell
Fig. 4. Normal X chromosome and isochromosome Xq: 46,X,i(X)(q10) in a patient with Turner syndrome.
Brackets indicate region of duplication on Xq.
subsequent reunion of the sister chromatids. The i(Xq)s are equally likely to be maternal or paternal
(45). The error occurs during male or female gametogenesis. When the error occurs postzygotically,
it is likely to be at the first postzygotic division because 45,X/46,XX/46,Xi(X)(q10) mosaics are
extremely rare (45).
These patients are phenotypically indistinguishable from those with pure 45,X, although there
have been reports of an increased risk of autoimmune problems in patients with an isochromosome X
(59). In a study of 145 women with Turner syndrome, 83% with an X isochromosome had positive
thyroid autoantibodies compared with 33% of women with other karyotypes. The isochromosome-X
women were also more likely to become hypothyroid and require thyroxine (60).
RING X
A subset of patients with Turner syndrome, estimated at approximately 15%, have one normal X
chromosome and a ring X, most often as a mosaic cell line (45). In a study of patients with a 45,X/46,X,r(X)
karyotype in whom the parental origin of the ring could be determined, the ring was derived from the
opposite parent from the normal X. In one patient, there was uniparental disomy (UPD) for the X
chromosome (see Chapter 19). In two-thirds of patients, the normal X was maternal in origin, and in
one-third of patients, it was paternal, as it is in 45,X patients (61). The size of the ring varies from
minute to nearly the size of a normal X. An important first step in characterizing a ring is to perform
FISH (see Chapter 17) with a painting probe for the X to confirm that it is derived from the X and not
Y (62) (see the section Mosaicism with a Y Chromosome).
In general, ring X patients lack many of the classic somatic features of Turner syndrome (63).
Those with ring X often do not have lymphedema and, therefore, are less often ascertained at birth
compared to 45,X individuals (64). Although some have typical features of Turner syndrome, others
have a severe phenotype with mental retardation, facial dysmorphism, and congenital malformations.
Some patients with a ring X and severe phenotype have features similar to those of patients with
Kabucki syndrome, a multiple malformation syndrome (63). El Abd et al. reported a characteristic
behavioral profile in five patients with a small active ring X that included autisticlike features, obsessive
compulsive behavior, and social and communication problems (65).