Dir dup(X) (q13-->qter) in a girl with growth retardation, microcephaly, developmental delay, seizures, and minor...

In males, duplication of a portion of Xq is associated with multiple congenital anomalies and developmental delay. Most females recognized as having dup(Xq) are phenotypically apparently normal relatives of phenotypically abnormal males; phenotypic normalcy has been attributed to selective inactivation of the duplicated X chromosome. Heretofore, apparently only 5 distinctly phenotypically abnormal females with dup(Xq) have been reported. We report on a 3-year-old girl with developmental delay, growth retardation, microcephaly, minor anomalies, and a seizure disorder who had a nonmosaic, de novo direct duplication of the terminal portion of one X chromosome. In each of 50 lymphocytes examined, the duplicated X chromosome was found to be late-replicating. This case shows that selective inactivation (as reflected by late replication) of the duplicated X chromosome does not inevitably confer phenotypic normalcy on females with dup(Xq), and suggests that other mechanisms must account for the phenotypic differences observed among females with dup(Xq), such as expression of recessive genes on the active X chromosome, incomplete inactivation of some portion of the duplicated chromosomal segment, an imprinting effect, or some combination of these.