Angelman Syndrome

Angelman Syndrome (AS) is a very rare (estimated 1 in 15 000) neurogenetic disorder characterized by a severe global developmental delay. People living with AS have little or no verbal skills, poor gross and fine motor skills, and possible seizure and sleep disorders. 

There are a various genetic changes that cause AS:deletion of the q11-q13 region of maternal chromosome 15, a uniparental disomy or UPD (meaning 2 copies of the father’s chromosome 15), or an imprinting mutation. Kate is deletion positive. 

Deletions are not inherited, as they are errors in the DNA that are made during sex cell reproduction. If this happens to a mother’s eggs, it happens when the mother herself was a 5 month old fetus. Deletions happen ALL the time in sex cell reproduction – they just usually happen in what we call non-sense DNA, or DNA that doesn’t code for anything, so the body tolerates them. Geneticists estimate that most people have deletions in their genome. Some deletions that are in sensible DNA (or DNA that codes for genes) are small enough that they don’t cause too much of a change in the protein product of the transcribed and translated gene. In the case of AS, a deletion happens on the UBE3A gene, which codes for an important brain protein called ubiquitin ligase. AS is one of the few human disorders susceptible to genetic imprinting. Most people have 2 copies of every chromosome; one from mom, one from dad. Normally, if there’s an error in a gene, your body expresses the healthy copy instead of the bad one. But this is not the case in AS. Only the maternal copy of chromosome 15 is expressed in the brain and in AS, it’s either missing (UPD) or a portion of it is deleted. Its sad because there’s a healthy copy of the UBE3A gene sitting on the paternal chromosome, but the brain won’t express it. 

The Angelman spectrum is very broad.  Each child is different from the next. There are no guarantees that Kate will have all the symptoms of AS.