1 - Department of Medical Genetics, Hospital Dona Estefânia, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
- American Society of Human Genetics Virtual Meeting October 2021 (Poster)
Resumo:
Background: Small supernumerary marker chromosomes (sSMCs) are rare cytogenetic abnormalities, present in less than 0.08% of all pregnancies. sSMCs are extra chromosomes with structural anomalies whose size is smaller than or equal to that of chromosome 20 on the same metaphase spreads. Reportedly, about 70% of cases of sSMCs are de novo and most frequently derived from chromosome 15.Uniparental disomy (UPD) is the inheritance of both homologous chromosomes from the same parent. The most prominent clinical outcome of UPDs are imprinting disorders, and when affecting chromosome 15, is associated with Prader-Willi or Angelman syndromes.
Case Presentation: We report a 39-year-old woman that underwent amniocentesis at 16 weeks of gestation, due to high risk for trisomy 21 (1/88) at first trimester combined screening. Ultrasound performed at 21 weeks and 5 days of gestation showed bilateral clubfoot. Conventional cytogenetics identified an abnormal fetal karyotype: 47,XY,+mar[7]/46,XY[10]. Parents had normal karyotypes. Fetal chromosomal microarray (CMA) analysis was normal. Fluorescence in situ hybridization (FISH) revealed a marker-chromosome del(15)(q10), consisted exclusively of heterochromatic material. UDP studies indicated maternal UDP of chromosome 15, establishing the diagnosis of Prader-Willi syndrome. After genetic counseling, parents decided on the termination of pregnancy.
Discussion: Identification of sSMC is a difficult task in prenatal diagnosis (PND). Conventional karyotype analysis can detect numerical and structural chromosomal abnormalities but cannot determine the origin and genetic content of sSMCs. The identification of a sSMC in prenatal settings must alert clinicians to a possible UPD. Prenatal UPD testing should be considered, among other criteria, when a structurally abnormal chromosome 15 or a de novo sSMC with no apparent euchromatic material in the fetus are identified.
Conclusion: We bring to attention the importance of combining cytogenetic and molecular genetic techniques to the detailed characterization of marker chromosomes in PND. It allows proper genetic counseling, facilitates informed decision-making, prevents uncertainty, and provides proper prognostic assessments.
Palavras Chave: Imprinting Chromosomes, Prenatal Diagnosis, Small supernumerary marker chromosomes, Uniparental disomy