Familial complex chromosomal rearrangement in a dysmorphic child with global developmental delay

Area of Science:

• Human Genetics
• Clinical Cytogenetics
• Reproductive Genetics

Background:

• Familial complex chromosomal rearrangements (CCRs) are rare genetic conditions involving multiple chromosome breakpoints.
• Understanding the inheritance patterns and clinical manifestations of CCRs is crucial for genetic counseling and reproductive planning.
• Chromosomal abnormalities are a significant cause of developmental delay, infertility, and recurrent spontaneous abortions.

Observation:

• A dysmorphic child presented with global developmental delay attributed to a de novo supernumerary marker chromosome.
• Karyotyping and fluorescence in situ hybridization (FISH) revealed the marker arose from malsegregation of a familial CCR involving chromosomes 7, 12, and 14.
• The balanced form of this CCR was present in the child's mother, maternal grandmother (history of recurrent miscarriages), and maternal uncle (infertility).

Findings:

• This is the first reported case of a familial CCR involving chromosomes 7, 12, and 14.
• The study demonstrates how a familial CCR, when passed down, can lead to distinct clinical outcomes including developmental delay and reproductive issues.
• Malsegregation of the balanced CCR resulted in a supernumerary marker chromosome, causing the proband's phenotype.

Implications:

• This case highlights the critical role of comprehensive chromosomal analysis in diagnosing developmental delay and dysmorphism in children.
• It emphasizes the importance of investigating familial chromosomal rearrangements in cases of recurrent spontaneous abortions and unexplained infertility.
• Genetic testing for CCRs can aid in accurate diagnosis, family planning, and risk assessment for affected families.