Inherited ring chromosomes: an analysis of published cases

Area of Science:

• Genetics
• Human Genetics
• Chromosomal Abnormalities

Background:

• Ring chromosomes are rare chromosomal abnormalities.
• Inherited ring chromosomes are even rarer than de novo occurrences.
• Previous estimates of inherited ring chromosome prevalence are limited.

Purpose of the Study:

• To review and estimate the proportion of inherited ring chromosomes.
• To analyze clinical manifestations in familial cases of ring chromosomes.
• To inform genetic counseling practices for carriers of ring chromosomes.

Main Methods:

• Systematic review of published case reports involving ring chromosomes.
• Calculation of the proportion of inherited versus de novo ring chromosomes.
• Comparison of clinical phenotypes between carrier parents and affected offspring.

Main Results:

• Identified 30 individuals with inherited ring chromosomes from 23 carrier parents.
• Estimated the upper limit of inherited ring chromosomes at 5.6%, with a likely true proportion of ~1% due to survival and publication bias.
• Observed mosaicism in both parent and child in 9 of 30 transmitted ring cases, suggesting inherited chromosomal instability.
• Found that familial cases often exhibit milder clinical manifestations than typical ring chromosome cases.
• Noted that offspring phenotypes ranged from similar to the parent to more severe (particularly mental impairment) in about a third of cases.

Conclusions:

• Inherited ring chromosomes represent a small fraction of all ring chromosome cases.
• Familial transmission of ring chromosomes can lead to variable and potentially severe clinical outcomes in offspring.
• Genetic counseling for individuals carrying ring chromosomes must consider the risk of more severe phenotypes in subsequent generations.