A rare de novo prenatal case of Down syndrome due to der(21;21)(q10;q10)

Abstract

Down syndrome (DS) is the most common chromosomal abnormality in the human population, most frequently caused by trisomy 21 due to meiotic nondisjunction. Rarely, DS may result from an isochromosome or a Robertsonian translocation, this being the least common variant. We present a rare prenatal case of Down syndrome caused by a derivative chromosome 21, together with a case-based review of previously reported prenatal der(21;21)/i(21q) rearrangements. We report a case of prenatal diagnosis of DS in a 13-week female fetus, characterized by a derivative chromosome 21, der(21;21)(q10;q10), identified by conventional karyotyping and subsequently confirmed by fluorescence in situ hybridization (FISH). First-trimester ultrasonography showed bilateral jugular lymphatic sacs, marked tricuspid regurgitation, and a single umbilical artery. Quantitative fluorescence polymerase chain reaction (QF-PCR) failed to detect the structural chromosomal abnormality. The rearrangement was considered likely de novo based on normal parental karyotypes. Consequently, the empirical recurrence risk is 1% for de novo cases, whereas in families with a parental 21q;21q rearrangement the recurrence risk may approach 100%. This case highlights the importance of integrating detailed ultrasound screening with molecular and cytogenetic techniques, including QF-PCR, conventional karyotyping, and FISH, for accurate prenatal diagnosis of DS. Precise determination of the underlying chromosomal abnormality is essential for providing accurate genetic counseling, estimating recurrence risk, and facilitating informed reproductive planning for the parents.