Magnesium Supplement and the 15q11.2 BP1-BP2 Microdeletion (Burnside-Butler) Syndrome: A Potential Treatment?

Abstract

The 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome is an emerging disorder that encompasses four genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5). When disturbed, these four genes can lead to cognitive impairment, language and/or motor delay, psychiatric/behavioral problems (attention-deficit hyperactivity, autism, dyslexia, schizophrenia/paranoid psychosis), ataxia, seizures, poor coordination, congenital anomalies, and abnormal brain imaging. This microdeletion was reported as the most common cytogenetic finding when using ultra-high- resolution chromosomal microarrays in patients presenting for genetic services due to autism with or without additional clinical features. Additionally, those individuals with Prader-Willi or Angelman syndromes having the larger typical 15q11-q13 type I deletion which includes the 15q11.2 BP1-BP2 region containing the four genes, show higher clinical severity than those having the smaller 15q11-q13 deletion where these four genes are intact. Two of the four genes (i.e., NIPA1 and NIPA2) are expressed in the brain and encode magnesium transporters. Magnesium is required in over 300 enzyme systems that are critical for multiple cellular functions, energy expenditure, protein synthesis, DNA transcription, and muscle and nerve function. Low levels of magnesium are found in those with seizures, depression, and acute or chronic brain diseases. Anecdotally, parents have administered magnesium supplements to their children with the 15q11.2 BP1-BP2 microdeletion and have observed improvement in behavior and clinical presentation. These observations require more attention from the medical community and should include controlled studies to determine if magnesium supplements could be a treatment option for this microdeletion syndrome and also for a subset of individuals with Prader-Willi and Angelman syndromes.

Keywords: 15q11.2 BP1–BP2 microdeletion (Burnside–Butler syndrome); CYFIP1; NIPA1; NIPA2; Prader–Willi and Angelman syndromes; TUBGCP5 genes; magnesium transporters and supplementation; potential treatment options.

Figure 1

Chromosome 15 ideogram showing the location of genes and transcripts causing Prader–Willi syndrome (PWS) that are imprinted and paternally expressed (blue) and Angelman syndrome (AS) which are imprinted and maternally expressed (red). The location and size of the 15q11.2 BP1–BP2 microdeletion, the typical larger 15q11–q13 type I deletion involving breakpoints BP1 and BP3, and the typical smaller 15q1–q13 type II deletion involving breakpoints BP2 and BP3 are illustrated. IC: imprinting center controlling the activity of imprinted genes in the 15q11–q13 region.