Dicentric Recombinant Chromosome 18 due to Maternal Paracentric Inversion Analyzed by Array CGH

Area of Science:

• Human Genetics
• Clinical Cytogenetics
• Reproductive Genetics

Background:

• Chromosomal abnormalities affect 0.5-0.8% of live-born infants, often causing developmental and morphological defects.
• Paracentric inversions are intrachromosomal rearrangements that can lead to chromosomally unbalanced gametes in carriers.

Observation:

• A 3-year-old girl presented with multiple congenital abnormalities, severe intellectual disability, and motor retardation.
• Clinical features included microcephaly, bilateral cleft lip and palate, hearing loss, and cardiac defects.
• Karyotype analysis revealed a dicentric rearrangement of chromosome 18 (dic(18)), confirmed by FISH.
• Maternal karyotype showed a paracentric inversion in chromosome 18 (inv(18)(q11.2?q21.3?)).

Findings:

• Array comparative genomic hybridization (CGH) identified duplications at 18p11.32p11.21 and 18q11.1q11.2, and a deletion at 18q21.33q23.
• The patient's final karyotype is arr 18p11.32p11.21(x3), 18q11.1q11.2(x3), 18q21.33q23(x1).

Implications:

• This is the first reported case of a dicentric chromosome 18 arising from a maternal paracentric inversion.
• The study highlights the importance of investigating parental karyotypes in cases of complex chromosomal rearrangements.
• Understanding genotype-phenotype correlations in such rare conditions is crucial for genetic counseling and clinical management.