Prenatal to postnatal outcomes in a whole maternal isodisomy 6: a case report with favorable prognosis and literature review

Whole maternal isodisomic uniparental disomy of chromosome 6 (UPiD6) is extremely rare, associated with various clinical manifestations and few favorable outcomes have been reported. We investigated a prenatally diagnosed fetal case with whole maternal UPiD6 (UPiD(6)mat) and reviewed literature of maternal UPD6 (UPD(6)mat). A female fetus with microdeletion and microduplication of chromosome 6 by non-invasive prenatal test (NIPT) subsequently diagnosed with whole UPiD(6)mat was selected as the study subject. The amniotic fluid karyotype was normal. Except whole maternal UPiD6, no pathogenic copy number variations (CNVs) and pathogenic sequence variants was found by chromosomal microarray analysis (CMA) and trio whole exome sequencing (ES), respectively. After genetic counseling, the parents opted to continue the pregnancy. Except intrauterine growth restriction (IUGR) from 26 weeks in gestation period and catch-up growth at postnatal stages, no major anomalies were found at her 27-month age. CMA of multiple placental samplings demonstrated mosaicism of large-segment deleterious deletions or duplications of chromosome 6p which was consistent with NIPT results while CMA of umbilical cord showed UPD6. Additionally, placental pathology showed dysplasia and infarctions. Previously reported UPD(6)mat cases were reviewed for prenatal and postnatal features. Literature review of 26 cases of UPD(6)mat identified IUGR in 23 (88.5%), which often with single-gene disorders and poor prognosis. Importantly, in prenatally diagnosed whole UPiD(6)mat fetuses, after rigorous exclusion of pathogenic CNVs/SNVs by CMA/whole ES and in the absence of major structural anomalies, a relatively favorable postnatal early prognosis may be achievable under close multidisciplinary management. However, this conclusion must be strictly limited to this specific subset and does not apply to UPD6 cases with unmasked recessive disorders or other chromosomal abnormalities.