Burnside-Butler Syndrome: A Diagnosis in Neurodevelopmental Delay

The authors report a 15-year-old Caucasian male, with a history of learning/intellectual disability (very low verbal and full-scale IQ (﹤70)), combined type attention-deficit/hyperactivity disorder (ADHD), an unusual happy appearance, overweight, mild tricuspid valve regurgitation and facial pilosity asymmetry. Karyotype XY, 46 and PCR revealed a FMR1 allele of normal size. Through microarray analysis, he was identified with a copy number variation - a 537Kb deletion between BP1 and BP2 on 15q11.2, involving various genes, including CYFIP1, TUBGCP5, NIPA1 and NIPA2.

Patients with 15q11.2 BP1-BP2 microdeletion (termed Burnside-Butler) syndrome, according to recent literature, can present with developmental delay (speech delay, writing and reading difficulties, verbal IQ ≤75) and neurobehavioral abnormalities including ADHD and unusual happy expression; less commonly, patients present mild dysmorphic features and congenital heart defects. These features are present in our patient. However, overweight or obesity have not been directly associated. Specific involvement of facial pilosity or tricuspid valve defects have not been previously described in this emerging cytogenetic syndrome, whose phenotypic features are still in expansion.

The authors aim to further the awareness of this etiologic entity, believing that achieving a diagnosis offers a basis on which to delineate the approach both to the patient and to their families, who in this case were oriented to Medical Genetics evaluation.