We were talking about developmental pathology the other day in class – trisomies, sex chromosome numerical abnormalities, microdeletion syndromes etc. – and the term “uniparental disomy” came up. Someone asked, what is that, and how do you get it? Great question! Before we get to the answer, let’s take a look at some of the syndromes that are caused by this abnormality.

The most well-known syndromes caused by uniparental disomy are Prader-Willi and Angelman syndromes. These are both microdeletion syndromes, meaning that the patient has a little deletion within a chromosome that is so tiny that it is often not visible by regular G-banding techniques (you need to use FISH).  Both Prader-Willi and Angelman syndromes are caused by tiny deletions in chromosome 15. The interesting thing is that if the deletion is in dad’s chromosome 15, the baby develops Prader-Willi syndrome, but if the deletion is in mom’s chromosome 15, the baby develops Angelman syndrome. Patients with these syndromes have uniparental disomy, meaning that they have inherited both copies of the abnormal chromosome 15 from one parent (instead of one from mom and one from dad). We’ll discuss how this can happen in a minute.

The two syndromes are surprisingly different. Patients with Angelman syndrome have mental retardation, a jerky, puppet-like gait, inappropriate outbursts of laughter, and severe speech problems. Patients with Prader-Willi syndrome have poor muscle tone and poor feeding as babies, but later develop an obsession with food, resulting in extreme food-seeking behavior and obesity.

Back to the question. Uniparental disomy means that you inherit two copies of a particular chromosome from one of your parents, and no copy from the other parent. It can happen in three ways, all of which involve two consecutive mistakes in cell division.

1. Trisomic rescue. This happens when you get a trisomy (as happens when the chromosomes don’t split up the way they should during meiosis, and you end up with two copies of some chromosome from mom and one from dad – or vice versa), and then you lose one of those three chromosomes (the “odd one out”, the lone one from one of the parents). You’re left with two chromosomes from one parent, and none from the other.

2. Monosomic rescue. This happens when you have a monosomic zygote (only one copy of a particular chromosome – the other parent’s dropped out), and that chromosome duplicates itself.

3. Gamete complementation. This is when you have a gamete with two copies of a chromosome (should have only one), and it gets fertilized with a gamete that happens to have no copies of that chromosome.

Here’s a good reference. The more I read about this stuff, the more amazed I am that things usually go right.

The image above is “Boy with a Puppet” or “A child with a drawing” by Giovanni Francesco Caroto. Dr. Harry Angelman, a pediatrician working in England, first reported three children with what is now known as Angelman syndrome in 1965. While vacationing in Italy, Angelman saw the painting.  The boy’s laughing face reminded him of his three patients, as did the puppet in the drawing, which reminded him of the fact that all three patients exhibited jerky movements. He subsequently described the children with this syndrome as “puppet children,” a title that was obviously not very pleasing. The name of the syndrome was later changed to Angelman syndrome.