The Principles of Clinical Cytogenetics - Extra Materials - Springer

Sex Chromosomes and Sex Chromosome Abnormalities 229
Fig. 7. Derivative X chromosome consisting of a small terminal Xp deletion and translocation of Yq:
46,X,der(X)t(X;Y)(p22.3;q11.2) mat. This was seen in a 5-year-old girl with short stature who had inherited the
chromosome from her mother, who also had short stature but was otherwise normal. Brackets indicate regions
on X and Y making up the derivative X.
12 of the patients for whom information was provided on intelligence were mentally retarded. Minor
facial anomalies, including flat nasal bridge and hypertelorism, were also reported. Four patients had
short limbs compatible with the diagnosis of chondrodysplasia punctata, presumed secondary to
nullisomy for the X-linked chondrodysplasia punctata gene on Xp (CDPX). In two adult males,
azoospermia and small testes were reported. The size of the Xp deletion varies, and phenotypes
reflect which genes on Xp are missing. Short stature is a consistent finding; hypogonadism with
infertility is common. Patients can have short stature with or without Leri–Weill dyschrondrostosis
(as a result of SHOX deletion), chondrodysplasia punctata (CDPX deletion), mental retardation (presumed
MRX locus deletion), ichthyosis (STS deficiency), and hypogonadotrophic hypogonadism in
combination with anosmia (Kallmann syndrome) when the deletion is large and encompasses all of
the genes in this region (227).
With probes for the STS and Kallman syndrome regions on Xp, it is now possible to use FISH (see
Chapter 17) to delineate the extent of deletions of Xp22. This will be important in helping to predict
phenotype, especially in prenatally diagnosed cases.
Type 2 patients had a translocation of Yq11.2 → Yqter onto Xp22.3, with one normal X chromosome
and a derivative X: 46,X,der(X)t(X;Y)(Xqter → Xp22.3::Yq11.2 → Yqter) (see Fig. 7). Most
of these women were ascertained through sons with a type 1 translocation. All 25 reported cases were
phenotypic females, and 17 of 22 with height information were short. Most had proven fertility or
reportedly had normal ovaries (226). Most have normal intelligence, but mild mental retardation has
been reported (228).
Type 3 patients had one normal X chromosome and a second sex chromosome that was dicentric,
consisting of major portions of both X and Y: 46,X,dic(X;Y)(Xqter → Xp22.3::Yp11.2 → Yqter).
All three patients reported were phenotypic males and had short stature and hypogonadism or
azoospermia (226).