invdup(8)(8q24.13q24.3)-A Complex Alteration and Its Clinical Consequences.

Area of Science:

• Genetics
• Human Molecular Genetics
• Clinical Genetics

Background:

• Structural variations, such as chromosomal duplications, are significant contributors to genetic diversity and can lead to pathogenic outcomes.
• Understanding the precise impact of specific structural variations on phenotype is crucial for diagnosing and managing genetic disorders.

Observation:

• Two cases, a mother and son, presented with identical partial inverted duplications of chromosome 8 long arm [invdup(8)(q24.21q24.21)] spanning 17.18 Mb.
• The son displayed microcephaly, hypertrichosis, seizures, and developmental delay, while the mother showed cleft lip/palate, down-slanted palpebral fissures, and learning disabilities.

Findings:

• The identical chromosomal duplication resulted in markedly different clinical presentations between the mother and son.
• This phenotypic variability suggests that factors beyond the primary structural variation, potentially including other genetic modifiers or epigenetic influences, contribute to the observed clinical outcomes.

Implications:

• The study underscores the complexity of genotype-phenotype correlations in cases of structural chromosomal abnormalities.
• Further research into the specific genes within the duplicated region and potential modifier genes is warranted to elucidate the mechanisms behind the differential clinical manifestations.
• This case series emphasizes the need for comprehensive genetic evaluation and counseling for families with recurrent or complex structural variations.