Today we will talk about Genetic Testing and subtypes of PWS.
How is PWS diagnosed?
PWS is diagnosed with a blood test that looks for the genetic abnormalities that are specific to PWS – called a “methylation analysis.” A FISH (flourescence in-situ hybridization) test identifies PWS by deletion, but it does not diagnose other forms of PWS. The methylation test will identify all types of PWS and is the preferred test for diagnosis. If a methylation test is done first, additional testing may be needed to determine whether PWS is caused by a paternal deletion, UPD, or an imprinting mutation. In cases where an imprinting mutation is suspected, blood may also be drawn from the parents.
What causes Prader-Willi syndrome?
PWS is caused by a lack of active genetic material in a particular region of chromosome 15 (15q11-q13). Normally, individuals inherit one copy of chromosome 15 from their mother and one from their father. The genes in the PWS region are normally only active on the chromosome that came from the father. In PWS, the genetic defect causing the inactivity of chromosome 15 from the father (paternal chromosome 15) can occur in one of three ways:
PWS by Deletion
Most often, part of the chromosome 15 that was inherited from the person’s father is missing, or deleted, in this critical region. This small deletion occurs in approximately 70% of cases and usually is not detectable with routine genetic analysis such as amniocentesis.
PWS by UPD
Another 30% or so of cases occur when an individual inherits two chromosome 15s from their mother and none from their father. This scenario is termed maternal uniparental disomy (UPD).
PWS by Imprinting Mutation
Finally, in a very small percentage of cases (1-3%), a small genetic mutation in the Prader-Willi region causes the paternal chromosome 15 genetic material (although present) to be inactive.
Kemett has UPD. We had genetic testing done while in NICU with a geneticist and also had neurological testing done. They had no idea what was going on with Kemett. We’d go up one day and be told he was doing great, and then go up an hour later and another doctor would tell us he might die soon. It was terrible. I finally had a doctor tell me to not google the tests they were doing- they were all spectrum- and concentrate on Kemett. He was our baby and would always be our child first. That really helped me turn around my thinking, and concentrate on Kemett and not what his diagnosis might be.
We were released prior to tests coming in, and met with the geneticist a week or so after. We were relieved to find out Kemett did not have SMA or myotonic distrophy. She was pretty sure it was PWS but we needed further testing. This was then lost for 8 weeks and we were lied to about this. Once we figured it out, we finally found out he had PWS- UPD subtype.
We were scared when we first found out what he had when we googled it. Do NOT google PWS. We soon found blogs from parents whose kids were doing great! We felt so much better. And having a diagnosis allowed us to get started, set doctors appointments, meet parents online, etc.
See you tomorrow!