Chromosome 15q overgrowth syndrome: prenatal diagnosis, molecular cytogenetic characterization, and perinatal findings in a fetus with dup(15)(q26.2q26.3)

Objective: To present molecular cytogenetic characterization of a prenatally detected duplication of 15q26.2→q26.3 in a fetus with overgrowth.

Case report: A 34-year-old para 0 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 15, or der(15), with additional material at the end of the long arm of one chromosome 15. Parental karyotypes were normal. Fetal overgrowth was first noted at 21 weeks of gestation. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization revealed a 4.71-Mb duplication from 15q26.2 to 15q26.3 encompassing the IGF1R gene. Fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone probes specific for 15q26.2-q26.3 and the subtelomeric region of 15q showed a direct duplication and no terminal deletion in the der(15). Polymorphic DNA marker analysis determined a paternal origin of the duplication of 15q. Level II ultrasound at 23 weeks of gestation revealed a fetal biometry equivalent to 26 weeks. The pregnancy was subsequently terminated, and a 1062-g (>99(th) centile) malformed fetus was delivered at 24 weeks of gestation with craniofacial dysmorphism, craniosynostosis, and overgrowth.

Conclusion: The present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2→q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.