De Novo Mosaic 6p23-p25.3 Tetrasomy Caused by a Small Supernumerary Marker Chromosome Presenting Trisomy Distal 6p Phenotype: A Case Report and Literature Review

Area of Science:

• Genetics
• Human Genetics
• Clinical Genetics

Background:

• Small supernumerary marker chromosomes (sSMCs) are rare chromosomal abnormalities with largely unknown clinical significance.
• sSMCs derived from the chromosome 6 short arm (sSMC(6)) are particularly rare, with no reported cases lacking centromeric DNA.

Observation:

• A de novo mosaic sSMC was identified in a male infant presenting with small for gestational age, microcephaly, facial dysmorphism, congenital eye defects, and multi-system malformation.
• Cytogenetic analysis revealed a mosaic karyotype (47,XY,+mar [25]/46,XY [22]).
• Array comparative genomic hybridization (aCGH) confirmed mosaic tetrasomy for the distal 6p region (6p23-p25.3).

Findings:

• This is the first reported case of mosaic tetrasomy 6p23-p25.3 attributed to an inverted duplicated neocentric sSMC.
• The observed phenotype aligns with features of trisomy for the distal 6p region.
• The study highlights the potential triplosensitivity of the FOXC1 gene, implicated in anterior segment dysgenesis and renal anomalies.

Implications:

• Comparing phenotypes in trisomy and tetrasomy 6p cases can improve genotype-phenotype correlations and identify candidate genes.
• Anterior segment dysgenesis in infants with microcephaly, growth retardation, and systemic malformations may indicate chromosome 6p duplication.
• aCGH is recommended for evaluating syndromic diseases associated with suspected chromosome 6p duplications.