Prenatal Diagnosis, Ultrasound Findings, and Follow-Up Information of 1q21.1 Deletion and Duplication Syndromes: A Single-Center Case Series.

INTRODUCTION

The clinical phenotypes associated with 1q21.1 deletion or duplication syndromes vary considerably among individuals, and the underlying mechanisms remain poorly elucidated. Moreover, data on prenatal ultrasound findings in fetuses carrying these copy number variants are still limited. This study aimed to preliminarily evaluate the association between prenatal phenotypic features and 1q21.1 deletion/duplication syndromes.

METHODS

A retrospective analysis was performed on 16 cases diagnosed with 1q21.1 deletions and 13 cases with 1q21.1 duplications, employing single nucleotide polymorphism arrays (SNP-arrays).

RESULTS

The deletion fragment sizes of the 16 deletion cases ranged from 1.30 Mb to 2.18 Mb, with the overlapping region located at 146.5 Mb to 147.5 Mb, encompassing nine OMIM genes such as ACP6, BCL9, and CHD1L. The fragment sizes of the 13 duplication cases ranged from 0.87 Mb to 3.87 Mb, with the overlapping region located at 146.5 Mb to 147.0 Mb, encompassing a total of 4 OMIM genes, namely, BCL9, CHD1L, FMO5, and PRKAB2. Among the 16 fetuses with deletions, eight exhibited ultrasound-detected abnormalities. Specifically, three fetuses had urinary tract malformations, four were diagnosed with fetal growth retardation, three displayed lateral ventricle enlargement, and one had aortic stenosis. Of the 13 fetuses with duplication, six were found to have ultrasound abnormalities, including four fetuses with cardiovascular malformations, one fetus with fetal growth retardation, one fetus with widened posterior fossa, and one fetus with widened lateral ventricle. Among the 16 fetuses identified with deletions, nine pregnancies were electively terminated, while seven pregnancies were carried to term, resulting in normal births. During follow-up, one child was diagnosed with epilepsy, and another exhibited delays in language and motor development. In the cohort of 13 fetuses with duplications, four pregnancies were terminated, and nine proceeded to term, yielding normal births. However, follow-up assessments revealed that one child experienced hearing impairment and another demonstrated speech delays.

CONCLUSION

This study suggests that fetuses with prenatal 1q21.1 deletions may be associated with malformations of the urinary system, whereas those with 1q21.1 duplications are likely associated with cardiac malformations. For fetuses diagnosed with 1q21.1 deletions or duplications who present with a normal phenotype prenatally, it is essential to conduct close monitoring of their neurodevelopmental trajectory postnatally.