Prenatal diagnosis of 9q34.3 microdeletion-associated Kleefstra syndrome in a pregnancy complicated by polyhydramnios: A case report and literature review

Taiwan J Obstet Gynecol. 2024 Nov;63(6):948-952. doi: 10.1016/j.tjog.2024.06.013.

Abstract

Objective: Kleefstra Syndrome (KS) is a rare genetic disorder caused by a deletion at 9q34.3. Studies showed that various heart defects are observed in 41-43% of patients and abnormal features on brain imaging in 58-63%. To date, the prenatal phenotype in KS has yet to be defined.

Case report: We present the first prenatal diagnosis and chromosomal microarray analysis (CMA) of a case of 9q34.3 microdeletion in a fetus with increased amniotic fluid, supported by abnormal prenatal ultrasound findings, and confirmed via autopsy. CMA revealed a 2.1 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1, which is consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome.

Conclusion: When a fetus with normal karyotype presents with polyhydramnios or abnormalities noted during second-trimester prenatal ultrasound screening, CMA analysis can be considered as the next step to rule out or confirm the diagnosis of chromosomal or other genetic aberrations.

Keywords: Kleefstra syndrome; Polyhydramnios; Prenatal diagnosis.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 9* / genetics
  • Craniofacial Abnormalities* / diagnosis
  • Craniofacial Abnormalities* / genetics
  • Female
  • Heart Defects, Congenital / diagnosis
  • Heart Defects, Congenital / genetics
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics
  • Microarray Analysis
  • Polyhydramnios* / genetics
  • Pregnancy
  • Pregnancy Trimester, Second
  • Prenatal Diagnosis / methods
  • Ultrasonography, Prenatal*

Substances

  • EHMT1 protein, human
  • Histone-Lysine N-Methyltransferase

Supplementary concepts

  • Kleefstra Syndrome