Angelman Case Study ID’s Largest Chromosome 15 Deletion Reported
Man required LTS to prevent aspiration
A very large deletion on chromosome 15 — the largest yet reported — was identified as the underlying cause of a severe presentation of Angelman syndrome (AS) in a 19-year-old man, according to a recent case report.
While deletions on chromosome 15 are the most common cause of AS, they are usually smaller and associated with less severe disease.
The man had significant motor and intellectual disabilities and also required a procedure called laryngotracheal separation (LTS) to prevent aspiration, a serious complication wherein food or liquid is breathed into the airways or lungs instead of being swallowed.
The findings suggest “it may be possible to predict the severity of an individual AS patient’s condition by confirming the deletion size” on chromosome 15, according to the study’s researchers.
The case report, “Laryngotracheal separation surgery in a patient with severe Angelman syndrome involving a 19.3 Mb deletion on 15q11.2– q14,” was published in Clinical Case Reports.
AS is caused by genetic defects that result in a missing or dysfunctional UBE3A gene on chromosome 15.
While children inherit two copies of UBE3A, one from each parent, only the copy from the mother is active in some parts of the brain. The most common Angelman-causing genetic defect occurs when part of the maternal chromosome is missing.
While the deletion always includes the part of the chromosome where UBE3A resides, its overall size can vary, potentially leading to the loss of other genes that can affect symptom severity.
Profound disability reveals largest chromosome 15 deletion
The researchers in Japan reported the case of a 19-year-old man with severe AS who had been diagnosed with suspicion of AS at 13 months due to abnormal limb movements, sleep problems, and seizures. A deletion on chromosome 15 confirmed the diagnosis.
He was intermittently hospitalized throughout his childhood due to seizures, which remained poorly controlled, despite treatment.
The man shaowed profound motor and intellectual disabilities, including an inability to sit, or communicate verbally or nonverbally. He was bedridden and required “assistance in all aspects of daily life,” the researchers wrote.
Since age 16, he had had episodes of aspiration pneumonia, which is marked by inflammation and infection in the lungs due to aspiration. This occurred more than once every two months by age 18. Nonsurgical treatments, including a feeding tube through the nose, were unsuccessful. He also had severe scoliosis, or a sideways spine curvature, that could have contributed to the problem, the researchers noted.
LTS, a well-known anti-aspiration procedure that works by separating the respiratory tract from the digestion tract, was attempted.
Following it, the man was able to be weaned off tube feeding and could eat through his mouth. He remained free of aspiration pneumonia after a year.
Although the deletion AS type “is regarded as the most profound form of AS,” the researchers said that it’s not usually as severe as seen in this case.
Additional molecular testing was performed to better understand the extent of his chromosome 15 deletion, due to the unusual severity of his symptoms. Results showed a deletion larger than any that has been previously reported, the researchers noted.
While common AS deletions range from 5–7 megabases in size, this patient’s deletion was 19.3 megabases.
“We consider the unusual deletion length to be a key cause of the atypically profound symptoms and necessity for LTS,” the researchers wrote, noting that “large deletions are associated with severe phenotypes [disease traits] because of the involvement of several genes … that may influence phenotypic outcome.”