Trisomy Xp and partial tetrasomy Xq resulting from gain of a rearranged X chromosome in a female fetus: pathogenic or not?

TL;DR

A female fetus had a rearranged X chromosome, but the child developed normally, raising questions about how X chromosome abnormalities affect health.

Contribution

This case study provides insights into the phenotypic effects of X chromosome rearrangements and X inactivation.

Findings

The rearranged X chromosome was inactivated in all abnormal cells, potentially suppressing harmful effects.

The child showed normal physical development despite the chromosomal abnormality.

The case highlights the role of skewed X-inactivation in mitigating genomic imbalance effects.

Abstract

Cytogenetic analysis of chorionic villous sampling revealed a mosaic karyotype with gain of a rearranged X chromosome. Microarray and additional studies indicated that the rearranged X carried an inverted duplication, a deletion and a satellited Xqter. Gain of this rearranged X was confirmed by follow-up amniocentesis and postnatal cord blood sample. A full-term infant girl was delivered and showed normal physical findings at both birth and 21-month follow-up examinations. Late replication studies demonstrated that the rearranged X was inactivated in all abnormal cells analyzed. Skewed X-inactivation may suppress the potentially deleterious effects of genomic imbalance; however, gain of X chromosomes, particularly rearranged X chromosomes, often presents challenges for prenatal genetic counseling. The gradation of clinical phenotype severity generally correlates with the number of additional X chromosomes. However, the X chromosome regions responsible for the abnormal phenotypes are poorly understood. This case will further elucidate the phenotypic effects of X inactivation and X chromosome abnormalities.

Figures