Familial Constitutional Rearrangement of Chromosomes 4 & 8: Phenotypically Normal Mother and Abnormal Progeny.

Area of Science:

• Human Genetics
• Medical Genetics
• Reproductive Genetics

Background:

• Balanced chromosome translocations in carriers often present without overt phenotypic abnormalities.
• However, these translocations can lead to recurrent spontaneous abortions or offspring with birth defects due to unbalanced chromosome complements.

Observation:

• A case of three siblings from a non-consanguineous family with recurrent abortions in the mother, presenting with intellectual disability and minor facial/limb dysmorphic features.
• The mother was identified as a balanced translocation carrier (t(4;8)), while siblings appeared karyotypically normal.

Findings:

• Chromosomal microarray analysis in one sibling revealed a partial monosomy 8pter-p23 and a partial trisomy 4pter-p16.
• Phenotypic features were systematically recorded using Human Phenotype Ontology (HPO) terms and analyzed with the Phenomizer tool.

Implications:

• This case underscores the importance of molecular genetic analysis, such as chromosomal microarray, in identifying sub-microscopic unbalanced translocations.
• Accurate phenotyping using standardized ontologies is crucial for diagnosing rare genetic conditions with heterogeneous presentations.
• Identifying such genetic sub-entities can help move beyond diagnoses of idiopathic mental retardation.