Prenatal diagnosis of 15q13.3 deletion and duplication syndrome: what do we tell the prospective parents?

objectiveThis retrospective study analyzed ultrasound findings, single nucleotide polymorphism microarray (SNP array) results, pregnancy outcomes, and postnatal follow-up data in fetuses with 15q13.3 deletions or duplications.

methodsSix fetuses were diagnosed with 15q13.3 deletions and nine with 15q13.3 duplications via SNP array at the prenatal diagnosis center of a single tertiary medical center from August 2017 to December 2024. Maternal demographics, ultrasound findings, SNP array results, pregnancy outcomes, and follow-up information were comprehensively reviewed and analyzed.

resultsThe deletions sizes in the six deletions ranged from 744 Kb to 1.87 Mb, primarily involving genes such as MTMR15, MTMR10, TRPM1, KLF13, OTUD7A, and CHRNA7. The overlapping region was located between 31.9 Mb and 32.5 Mb. In the nine duplication cases, the fragment sizes ranged from 419 Kb to 2.13 Mb, with overlapping region located between 31.9 Mb and 32.4 Mb. Among the six cases of fetal deletions, three (50.0%, 3/6) exhibited ultrasound abnormalities. The observed ultrasound phenotypes primarily consisted of cardiovascular malformations, lateral ventriculomegaly, intrauterine growth retardation, cleft lip and palate, abnormal finger development, and polyhydramnios. In the nine cases with fetal duplications, four (44.4%, 4/9) showed ultrasound abnormalities, predominantly featuring cardiovascular malformations, corpus callosum hypoplasia, enlarged gallbladder, lateral ventriculomegaly, and increased nuchal translucency. Among the six deletions cases, parental origin testing was conducted for five cases, two were identified as maternally inherited and three were de novo. In the nine duplications cases, eight underwent parental origin testing, with five being inherited (three paternal and two maternal) and two were de novo. Follow-up assessments revealed that the Case 7 showed speech and motor developmental delays. Case 8 experienced seizure at four years of age. At 18 months, Case 13 was diagnosed with bilateral strabismus.

conclusionThis study conducted a preliminary assessment of the genotype and phenotype of fetuses with 15q13.3 deletions/duplications, expanding the phenotypic spectrum of this syndrome. The study suggests that prenatal 15q13.3 deletions and duplications may be associated with cardiac malformations and lateral ventriculomegaly, but lack phenotype specificity. Moreover, it is essential to closely monitor the neuropsychiatric development postnatally in fetuses with 15q13.3 deletions and duplications that exhibit normal phenotypes during the prenatal period.