49, XXXYY: Parental Origin, Occurrence, and Clinical Phenotypes.

Area of Science:

• Genetics
• Human Chromosome Abnormalities
• Reproductive Biology

Background:

• 49, XXXYY is a rare sex chromosomal aneuploidy with limited reported cases (11 worldwide).
• The parental origin of extra sex chromosomes and clinical manifestations are not well-defined.
• Understanding the etiology and phenotype is crucial for genetic counseling and patient management.

Purpose of the Study:

• To investigate the parental origin of extra sex chromosomes in a 49, XXXYY case.
• To identify genetic variations associated with the 49, XXXYY karyotype.
• To comprehensively review and compare clinical features of 49, XXXYY cases.

Main Methods:

• Genome-wide copy number variation analysis using next-generation sequencing.
• Short tandem repeat (STR) locus genotyping for parental origin determination.
• Systematic literature review and phenotypic comparison of 12 49, XXXYY cases.

Main Results:

• The patient presented with a 49, XXXYY karyotype without mosaicism.
• No pathogenic microdeletions or microduplications were detected on autosomes.
• STR analysis indicated two of the three X chromosomes originated from the father, suggesting paternal meiotic nondisjunction (XXYY sperm formation).

Conclusions:

• Paternal nondisjunction during meiosis I and II is a key factor in 49, XXXYY development.
• Clinical features commonly include intellectual disability, minor facial dysmorphies, and gonadal/endocrine issues.
• 49, XXXYY is a rare chromosomal disorder primarily characterized by cognitive and developmental challenges.