Proximal 4p deletion syndrome in a woman with intellectual disability: a case report and literature review

TL;DR

A Chinese woman with a rare 4p chromosome deletion is reported, offering insights into the genetic basis of proximal 4p deletion syndrome and its associated traits.

Contribution

This case report expands the clinical and genetic understanding of proximal 4p deletion syndrome by identifying potential causative genes and enhancing genotype-phenotype correlations.

Findings

The patient had an 11.7 Mb deletion in 4p16.2-p15.32 and a 1.25 Mb duplication in 16p13.13.

Genes DRD5, WFS1, CC2D2A, PROM1, and QDPR were linked to the patient's intellectual disability and ovarian dysfunction.

Overlap in the deleted region was found in 17 of 37 published cases, aiding genotype-phenotype correlation studies.

Abstract

Deletions in chromosome 4p can lead to two distinct phenotypes, Wolf-Hirschhorn syndrome (WHS) and proximal 4p deletion syndrome. While WHS, associated with distal deletions, has well-characterized phenotypic features, proximal 4p deletion syndrome, involving the 4p14-p 16.1 region, shows moderate manifestations, and its causative gene remains unknown with fewer reported cases. Here we report a Chinese case: a 21-year-old female with a peripheral blood chromosomal karyotype of 46,XX, del(4)(p15.3-p16). NGS-CNVA further revealed an 11.7 Mb deletion in the 4p16.2-p15.32 region and a 1.25 Mb microduplication in 16p13.13. She had ovarian dysfunction, and moderate Intellectual Disability(ID) without typical proximal 4p deletion phenotypes. Through analysis of Genecards and OMIM databases, we identified two neurodevelopmental genes DRD5 and WFS1, and four ovarian dysfunction-related genes WFS1, CC2D2A, PROM1, and QDPR, suggesting their roles in the patient’s manifestations. Additionally, a review of 37 published cases of proximal 4p deletion syndrome revealed 17 cases with an overlap in the deleted region with our case. This report not only enhances the recognition of this rare syndrome among clinicians but also provides a basis for further exploration of the potential causative genes, contributing to a better understanding of the genotype-phenotype correlations in proximal 4p deletion syndrome.

The online version contains supplementary material available at 10.1186/s13039-025-00735-2.

Figures