1p36 Deletion patients are lucky to have Lisa Shaffer PhD, FACMG devoting research and knowledge about this syndrome. She's a leading researcher looking at what's going on genetically with children like Whitney. Dr. Shaffer spent over an hour and a half with conference attendees on Friday morning presenting the basics of the syndrome to the many conference newcomers as well as the latest findings from her research team and answering questions. Here are some important notes from her presentation:
First case of 1p36 Deletion Syndrome reported in 1980, 14 cases between 1980 and 1997
6 new cases diagnosed in 1997 with 1p36 Deletions – the year Dr. Shaffer’s first paper on 1p36 Deletion Syndrome published
Children from all different ethnic backrounds can be affected. Common are similar facial features
All have some degree of mental retardation and developmental delays.
78% have hypotonia,
64% Speech Delay/ Nonverbal
42% Feeding Difficulties
17% Oropharyngeal dysphasia (trouble swallowing)
44% Structural Heart defects
47% Hearing Loss – both conductive and sensorineural have been recorded
34% Constipation Some other ulcers, discomfort
60% MRI abnormalities
Most deletions occur during egg production. However, the larger deletions tend to come from sperm production. Breakpoints tend to occur throughout the p arm of chromosome 1.
Starting in 1999, a group of kids were diagnosed with duplications and triplications of 1p. There are additional symptoms such as the suchers in the skull are already fused instead of large soft spots at birth.
Looking at deletions and duplications can help us find genes. That is, we can begin to see the effects of different portions of the genome based on their presence or absence in patients. This, in turn, can lead to solutions to seizures and other symptoms. We can also anticipate and treat certain medical problems.
We now know that the deletions are occurring during sperm and eggs are produced. It’s prior to meiosis in the progenitor cells. The deletions occur in the mother of the patient when the mother is born. This means there was nothing the mother did that caused the deletion.
Now we’re studying what it is that causes chromosomes to break. This will be difficult work because the breaks took place when the patient’s grandmother was carrying the patient’s mother.
In 2009 it was found that regions of the genome which aren’t supposed to connect up can recombine. When this happens in the wrong places this may be a cause of breakage and deletions.
Deletions can occur at the end of a chromosome (terminal which Whitney has) or in the middle (interstitial). 54% are terminal and 30 are interstitial. Others are translocations and complex rearrangements.
Microarray testing is now becoming the norm in genetic testing to diagnose 1p36 Deletion Syndrome.
Population frequency of 1p36 Deletion Syndrome was revised in 2003 to estimate 1 in every 5,000 newborns. The most common terminal deletion syndrome found thus far.
In 2008, a paper describing physical features significant enough to allow 1p36 Deletion diagnosis through ultrasound was published. Also, microarray genetic tests can be performed on genetic material obtained through amniocentesis.
John C. Carey, MD practices here in Salt Lake at the University of Utah Hospital. He’s an MD who has worked a good deal with cases of 1p36 Deletion Syndrome. The hope is to involve him with more work to have a more clinical aspect to studies.