Mild features of partial PAX3 deletion in patients with Waardenburg Syndrome in prenatal: case report and literature review

Qi Chen^*Lin ShiYunpeng ChenXinyu CaoYan Yang

• Zhenjiang Fourth Peoples Hospital and Zhenjiang Women and Children's Hospital, Zhenjiang, China

Background: Waardenburg syndrome (WS) is a group of autosomal-dominant hereditary disorders characterized by auditory-pigmentary abnormalities. Haploinsufficiency of the PAX3 gene is considered one of the pathogenic mechanisms involved. However, clinical phenotypes are difficult to predict precisely in fetuses harboring PAX3 haploinsufficiency. In this study, we reported a family with a PAX3 deletion encompassing the exons 1-4, in which the manifestations ranged from normal to mild abnormalities. Case presentation: A 22-year-old woman (gravida 2, para 0) was referred to our prenatal center at 18 weeks of gestation due to a history of congenital spina bifida in her previous pregnancy. Chromosomal analysis had been performed on fetal tissue after the termination of the previous pregnancy, as well as on amniotic fluid during the current pregnancy. A rare partial deletion of the PAX3 gene was identified and confirmed to be of paternal origin. A diagnosis of WS was established based on the clinical features of the father. However, the newborn in this second pregnancy showed normal phenotypes after birth. Conclusion: This work suggests that deletions encompassing the promoter and functional domains of the PAX3 gene functionally represented haploinsufficiency mechanism, which lead to variable clinical manifestations. These findings broaden our understanding of copy number variation (CNV) analysis and genetic counseling in prenatal settings. Additionally, the PAX3 gene should be considered a candidate gene in cases of auditory pigmentary abnormalities or neural tube defects of unknown etiology.