The Principles of Clinical Cytogenetics - Extra Materials - Springer

Sex Chromosomes and Sex Chromosome Abnormalities 227
Fig. 6. Distal paracentric inversion of Xq: inv(X)(q26q28) in a woman with normal phenotype and fertility.
Brackets indicate region involved in inversion.
of 3 patients with random or skewed inactivation had an abnormal phenotype and 9 of 22 cases with
selective inactivation of the duplicated X had an abnormal phenotype (195). The reason for the variable
phenotypes but similar inactivation patterns could be the result of differential patterns of inactivation
along the chromosome. The activation status of the material present in excess copy number
might be what differentiates females with normal phenotype from those with abnormal phenotype.
The functional disomy of genes might affect the phenotype (202).
Replication studies cannot distinguish phenotypically normal and abnormal females with Xq duplications
(193,199). Correlations of X inactivation pattern and phenotype in patients with small duplications
should be interpreted carefully (145).
Inversions of the X Chromosome
Paracentric Inversions
Paracentric inversions of the X chromosome (see Fig. 6) are relatively rare. There has been a wide
range of phenotypes described. In general, when long-arm paracentric inversions involve the critical
region at Xq13–26, females have some degree of ovarian dysfunction (203). When the inversion is
outside the critical region, normal phenotype and fertility have been reported (204), although there are
exceptions to this (205). There has also been variability in mental function in females, with some having
mental retardation and others with normal intelligence, even in the same family (206). Males can be
phenotypically normal or have mental retardation (205,207). Fertility in males is also variable (208,209).
Pericentric Inversions
Most females with pericentric inversions of the X have normal phenotypes and fertility
(210,213,214). However, pericentric inversions of the X have been reported in females with gonadal
dysgenesis and with mental retardation (211). Keitges et al. reported dizygotic twins with the same
pericentric X inversion (p11;q22) (211). One twin was phenotypically normal with normal intelligence
and menses and had random inactivation of the X. The other was mildly mentally retarded and
had psychiatric problems, irregular menses, minor anomalies, and selective inactivation of the
inverted X. Proposed explanations for these findings include different normal Xs, a nondetectable
deletion or duplication in the abnormal twin, or chance. This also raises the likelihood that the replication
pattern of the inverted X is a better predictor of fertility than the breakpoints. Interestingly,
females with random X inactivation are more likely to have normal fertility than those with skewed
inactivation of the inversion X (211). Offspring of females with pericentric inversions are at risk for
inheriting a recombinant chromosome with associated phenotypic abnormalities (210,213–215).