Burnside–Butler syndrome

Overview

Burnside–Butler syndrome, also known as 15q11.2 microdeletion syndrome, is a genetic condition caused by a small deletion on the long arm of chromosome 15. This deletion occurs in the 15q11.2 region, specifically between breakpoints BP1 and BP2, and includes four genes believed to play a role in brain development. The syndrome is associated with a wide range of neurodevelopmental and behavioral symptoms, though the presentation can be highly variable—from asymptomatic individuals to those with developmental delays and psychiatric disorders.

Causes

Burnside–Butler syndrome is caused by a microdeletion in the chromosome region 15q11.2, between breakpoints BP1 and BP2. This deletion typically involves four genes:

• NIPA1

• NIPA2

• CYFIP1

• TUBGCP5

The loss of one copy of these genes (haploinsufficiency) is thought to affect brain development and neuronal signaling. The condition can occur sporadically or be inherited in an autosomal dominant manner from a parent who may or may not show symptoms. Notably, this region is distinct from the areas deleted in more well-known syndromes like Prader–Willi and Angelman syndromes, which involve other parts of chromosome 15q11–q13.

Symptoms

The clinical presentation of Burnside–Butler syndrome varies significantly. Some individuals may be asymptomatic, while others may display multiple neurodevelopmental features. Common symptoms and characteristics include:

• Developmental delays, especially in speech and motor skills

• Intellectual disability (mild to moderate)

• Behavioral challenges, such as ADHD or autism spectrum disorder (ASD)

• Learning disabilities

• Speech and language delays

• Hypotonia (low muscle tone) in infancy

• Coordination or fine motor difficulties

• Psychiatric issues in some cases, such as anxiety or mood disorders

• Seizures (less commonly)

• Dysmorphic features (mild and non-specific, if present)

Due to the variability, many individuals may not receive a diagnosis unless a genetic test is performed during an evaluation for developmental or behavioral concerns.

Diagnosis

Diagnosis of Burnside–Butler syndrome typically involves genetic testing after clinical signs suggest a possible chromosomal abnormality. Key diagnostic methods include:

• Chromosomal microarray analysis (CMA) – the preferred test to detect microdeletions in the 15q11.2 region

• Multiplex ligation-dependent probe amplification (MLPA) – may also identify deletions in the relevant genomic area

• Family testing – to determine if the deletion is inherited or de novo

• Neurodevelopmental assessment – to evaluate cognitive, behavioral, and language development

Treatment

There is no cure for Burnside–Butler syndrome. Treatment is supportive and tailored to the specific needs of each individual. Common interventions include:

• Early intervention programs – including speech, occupational, and physical therapy

• Special education services – for learning disabilities and developmental delays

• Behavioral therapy – especially helpful for managing ADHD, autism, or mood disorders

• Psychiatric care – when needed, to address anxiety, depression, or other mental health concerns

• Seizure management – if seizures occur, standard antiepileptic treatments are used

• Genetic counseling – for families to understand inheritance and recurrence risks

Prognosis

The prognosis for individuals with Burnside–Butler syndrome is generally favorable, especially with early and appropriate intervention. Many individuals lead independent lives with proper support. However, challenges with learning, behavior, or social development may persist and require long-term strategies. The condition is often underdiagnosed due to its subtle features and variable expression. Continued research is needed to fully understand the impact of the 15q11.2 BP1–BP2 microdeletion and guide future treatment strategies.