Double supernumerary isodicentric chromosomes derived from 15 resulting in partial hexasomy

Area of Science:

• Genetics
• Human Genetics
• Molecular Genetics

Background:

• Supernumerary marker chromosomes (SMCs) are rare genetic abnormalities that can lead to various clinical outcomes.
• Chromosome 15 abnormalities are associated with several genetic disorders, including Prader-Willi and Angelman syndromes.

Observation:

• Two unrelated patients presented with two supernumerary marker chromosomes (SMCs) derived from chromosome 15, resulting in partial hexasomy.
• In family 1, double SMCs were diagnosed prenatally, did not involve the Prader-Willi/Angelman critical region (PWACR), and were transmitted from the mother to a phenotypically normal child.
• In family 2, de novo hexasomy involving the PWACR was observed in a patient with severe psychomotor retardation and other phenotypic features.

Findings:

• Partial hexasomy for chromosome 15 can occur through the presence of double SMCs.
• Maternal transmission of double SMCs is possible, potentially resulting in a phenotypically normal offspring.
• Hexasomy encompassing the PWACR is associated with severe developmental abnormalities.

Implications:

• This study highlights the variable phenotypic outcomes associated with chromosome 15 supernumerary marker chromosomes.
• The findings underscore the importance of genetic counseling and prenatal diagnosis for SMCs.
• Understanding the role of the PWACR in developmental disorders is crucial for diagnosis and potential therapeutic strategies.