Burnside–Butler syndrome is a name that has been applied to the effects of

microdeletion In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleoti ...

of DNA sequences involving four neurodevelopmental genes (

TUBGCP5 Gamma-tubulin complex component 5 is a protein that in humans is encoded by the ''TUBGCP5'' gene. It is part of the gamma tubulin complex, which required for microtubule nucleation at the centrosome. See also *Tubulin * TUBGCP2 * TUBGCP3 * TUBGCP4 ...

, CYFIP1,

NIPA1 Non-imprinted in Prader-Willi/Angelman syndrome region protein 1 is a protein that in humans is encoded by the ''NIPA1'' gene. This gene encodes a potential transmembrane protein which functions either as a receptor or transporter molecule, possib ...

, and

NIPA2 Non-imprinted in Prader-Willi/Angelman syndrome region protein 2 is a protein that in humans is encoded by the ''NIPA2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of ...

). Varying developmental and psychiatric disorders have been attributed to the microdeletion; however, the great majority of people with the deletion do not have any clinical features associated with it. More studies are needed to delineate the range of

clinical presentation In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the patient ...

. The 15q11.2 BP1–BP2 microdeletion (Burnside–Butler syndrome) was the most common cytogenetic abnormality found in a recent study using ultra-high resolution

chromosomal microarray analysis Comparative genomic hybridization (CGH) is a molecular cytogenetic method for analysing copy number variations (CNVs) relative to ploidy level in the DNA of a test sample compared to a reference sample, without the need for culturing cells. The ai ...

optimized for

neurodevelopmental disorder Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental ...

s of 10,351 consecutive patients presenting for genetic laboratory testing who had

autism spectrum The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...

disorders (ASD). It may represent an under-recognized contributor to the global prevalence of ASD, which is a common clinical manifestation of many rare

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

s, many of which can be identified by chromosome microarray analysis. The 15q11.2 BP1-BP2 microdeletion was reported to account for 9% of the top 85 genetic findings associated with neurodevelopmental disorders followed by the proximal 16p11.2 deletion syndrome (5%). However, the very high frequency of the deletion in unaffected population controls suggests that there is considerable ascertainment bias and that most people who have a neurodevelopmental condition and the deletion are likely to have an alternate cause for their symptoms. In a large population-based study, 1 in 292 people in the general population had this deletion. While the deletion was over-represented in cases vs controls (1 in 126 cases had the deletion) suggesting that it likely does contribute to neurodevelopmental problems in some individuals, the penetrance is likely to be very low. To understand this point, it is important to remember that affected individuals make up only a small proportion of the population. Assuming that 1% have intellectual disability, for example, this would imply penetrance of ~1.3% for the deletion - i.e. 98.7% of people with the deletion would have no symptoms as a result. This suggests that the term "Burnside–Butler syndrome" should be used with caution, if at all. In the context of low penetrance for a very common variant, it is not surprising that the features that have been attributed to the deletion are highly variable and inconsistent. No consistent set of features has been described that would meet the usual criteria for naming a syndrome, and the use of the term is likely to cause confusion.

References

Congenital disorders Syndromes {{genetic-disorder-stub