Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion 5(p15.1q35.1)

Area of Science:

• Human Genetics
• Clinical Genetics
• Developmental Biology

Background:

• Cri-du-chat syndrome is a genetic disorder caused by a deletion on the short arm of chromosome 5 (5p-).
• Partial trisomy 5q is associated with duplications on the long arm of chromosome 5 (5q+).
• Reciprocal translocations and inversions can lead to complex chromosomal rearrangements with varied clinical outcomes.

Observation:

• A male infant presented with a complex chromosomal rearrangement: 46,XY,rec(5),dup q,inv(5)(p15.1 q35.1)pat.
• The proband displayed facial dysmorphia and a cat-like cry, characteristic of cri-du-chat syndrome.
• Severe growth and developmental retardation, microcephaly, complex cardiovascular abnormalities, and inguinal hernia were observed.

Findings:

• The patient's phenotype, including severe growth/developmental retardation and microcephaly, was more pronounced than typically observed in isolated partial monosomy 5p or partial trisomy 5q.
• The combination of dup(5q) and inv(5)(p15.1q35.1) in a reciprocal rearrangement likely contributed to the exacerbated clinical presentation.

Implications:

• This case highlights the significant impact of complex chromosomal rearrangements on developmental trajectories.
• Understanding genotype-phenotype correlations in such cases is crucial for accurate diagnosis and genetic counseling.
• Further research into the functional consequences of dup(5q) and inv(5)(p15.1q35.1) is warranted to elucidate their roles in severe developmental disorders.