Random X-inactivation in a girl with duplication Xp11.21-p21.3: Report of a patient and review of the literature

We describe a 10-month-old girl with abnormal clinical findings and Xp duplication. She showed poor weight gain and developmental retardation, and had several minor anomalies including pigmentary dysplasia (hypomelanosis of Ito). She had a partial short arm duplication in the paternally derived X chromosome, 46,X,dup(X)(p11.21p21.3), with the normal and duplicated X chromosomes randomly inactivated. These findings indicate that gross functional imbalance in the cells with an active dup(X) chromosome has caused global developmental defects in the patient, and that functional chromosomal mosaicism with respect to the duplicated Xp region has resulted in pigmentary dysplasia. Literature review of 52 patients with partial X duplications revealed (1) random or skewed but not completely selective X-inactivation in 9 of 45 patients examined for the X-inactivation pattern, independently of the size or location of duplicated segments, (2) apparently normal phenotype in 6 of 9 patients with random or skewed X-inactivation, and (3) an abnormal phenotype in 13 of 35 patients with completely selective inactivation of dup(X) chromosomes.