Burnside–Butler syndrome

Lore & Background

The term Burnside–Butler syndrome arose from observations of a microdeletion on chromosome 15q11.2 between breakpoints BP1 and BP2, affecting four genes: TUBGCP5, CYFIP1, NIPA1, and NIPA2. Varying developmental and psychiatric disorders have been attributed to this deletion, but no consistent set of features has been described that would meet usual criteria for naming a syndrome. The deletion was found to be the most common cytogenetic abnormality in a large study of patients with autism spectrum disorders, accounting for 9% of the top 85 genetic findings associated with neurodevelopmental disorders, compared to 5% for the proximal 16p11.2 deletion syndrome.

Reader's Guide

The significance of Burnside–Butler syndrome lies in its illustration of the challenges in interpreting genetic variants with low penetrance. While the 15q11.2 BP1–BP2 microdeletion is over-represented in individuals with neurodevelopmental conditions compared to controls (1 in 126 vs. 1 in 292 in the general population), the vast majority of carriers show no symptoms. Assuming 1% of the population has intellectual disability, the penetrance of the deletion for that condition is estimated at only about 1.3%, meaning 98.7% of people with the deletion would have no symptoms. This low penetrance, combined with the high frequency of the deletion in unaffected controls, suggests considerable ascertainment bias and that most affected individuals with the deletion likely have an alternate cause for their symptoms. The article advises that the term 'Burnside–Butler syndrome' should be used with caution, if at all, as it may cause confusion and does not meet standard criteria for a named syndrome.

Did You Know?

• The 15q11.2 BP1–BP2 microdeletion was the most common cytogenetic abnormality found in a study of 10,351 consecutive patients with autism spectrum disorders.
• 1 in 292 people in the general population have this deletion, but only about 1.3% of carriers are estimated to develop intellectual disability.
• The term 'Burnside–Butler syndrome' is disputed because no consistent set of features has been described that meets usual criteria for naming a syndrome.