Prenatal diagnosis and follow up of a child with a complex chromosome rearrangement

Area of Science:

• Genetics
• Human Genetics
• Clinical Cytogenetics

Background:

• Balanced chromosomal rearrangements, including translocations and inversions, are typically associated with a low risk of adverse outcomes.
• De novo rearrangements, occurring spontaneously, require careful monitoring for potential phenotypic effects.
• Genetic amniocentesis is a prenatal diagnostic tool used to detect chromosomal abnormalities.

Observation:

• A rare case of a de novo, apparently balanced, three-way exchange translocation combined with a pericentric inversion was identified.
• The specific karyotype reported is 46,XX,t(6;11)(p21;q21),t(11;21)(q21;p13),inv(6)(p21q11).
• The chromosomal abnormality was detected via second-trimester genetic amniocentesis.

Findings:

• The child was phenotypically normal at birth with normal growth and motor development until 30 months.
• Subsequent to birth, the child experienced a drop in linear growth below the 5th centile and delayed speech development at 2 years of age.
• Despite the apparently balanced nature of the structural rearrangements, subtle phenotypic consequences emerged over time.

Implications:

• This case represents the first reported instance of a three-chromosome exchange involving a pericentric inversion identified through prenatal diagnosis.
• It underscores the importance of long-term follow-up for individuals with apparently balanced, complex chromosomal rearrangements.
• Further research may be needed to understand the specific mechanisms linking such complex rearrangements to developmental delays.