What causes RTS?

Once you've looked-up the symptoms of RTS, it's natural to ask what causes it. About one birth in every 100,000 has RTS. The European Commission defines a "rare disease" as a 1 in 2000 event, making RTS very rare. Little wonder the professionals don't seem to know much about it.

RTS is a genetic condition. We all have 23 pairs of chromosomes in all the cells of our body (excepting sperm and egg cells); half of each pair comes from your mother and half from your father. 

Each chromosome is made of chromatin, which looks like a string of beads: the string represents DNA and the beads represent nucleosomes. 

DNA (left), Chromatin (right)

Each nucleosome comprises a group of four histone protein pairs named: H2A, H2B, H3 and H4. The DNA winds twice around a nucleosome, gets 'fastened' by a H1 histone and then moves on to the next nucleosome.  

Nucleosome

The DNA of each chromosome is partitioned into genes - hundreds of them on each chromosome. Each gene encodes a unique sequence of amino acids which, in turn, define a specific protein in the cell. Our chromosomes contain about 26,000 genes, giving us a potential library of tens of thousands of proteins - each performing a special, often crucial, function. 

To be able to use a gene it needs to be switched-on or "expressed". This is done by unwinding the chromatin "string of beads", as shown in the middle of the Chromatin diagram above. When the beads are clumped together, as on the right of the diagram, the gene is made inaccessible and effectively switched-off or "silenced".

Usually, RTS is caused by the random mutation of one gene on a chromosome. About 60% of RTS cases are because the CREBBP gene on chromosome 16 mutates; about 3% of RTS cases are because the EP300 gene on chromosome 22 mutates. That leaves 37% of RTS cases for which the cause is, as yet, unknown. Clearly scientists need to do a bit more work before they understand the whole picture. 

Another cause of RTS is through family inheritance. If Maria were ever to have children with a non-RTS father, there'd be a 50% chance the offspring would have RTS. If the father had RTS then there'd be a 75% chance their children would have RTS. Even though RTS families are very rare, it made me wonder how Maria would feel about having children when she's an adult.

The more you learn about genetics, the more you discover that mutations are not uncommon. Some genetic mutations go unnoticed from birth but some, like mutations in the CREBBP gene, have a significant impact on the child because they affect several important body functions. 

Random mutations are just that, random. That means it's not my fault, it's not Joan's fault and it's certainly not Maria's fault that this arbitrary thing happened. It would be irrational to blame ourselves for the fact that Maria has RTS; doing that would be like blaming ourselves for not winning the Lottery. If I needed to blame something then its got to be God, or chance. Either way I'd be failing to appreciate the wonderful gift that chance or God has given us. Maria can't be helped by blame; she thrives when she's loved, and love is a potent epigenetic factor.

When a baby's born, the results are always a bit of a gamble: it may be a boy instead of a girl; it may look like your partner instead of you. Most of us expect these differences and accept them. We're surprised only when something unexpected happens. This can turn to shock when the unexpected becomes the unwanted; nobody wants a child to have RTS. 

For me, the shock was realising that Maria had a syndrome I knew nothing about and, as a consequence, she might never be "normal". I wondered which of the list of possible RTS symptoms Maria would potentially develop. 

But sometimes it just doesn't pay to be over-analytical. At present, Maria is actually quite fit medically. She's a very happy child (when she's not fighting with her sister) and has a great sense of empathy and humour. She loves to dance and sing. She's a walking dictionary of sign language (Makaton) and is slowly learning to speak. She's beautiful, both inside and out; and despite all the implications of the term "mental retardation", she's actually very clever. What more could you ask of a five year old child?

I always like to remind myself that if computer scientists were able to build a computer as "intelligent" as Maria, they'd be hailing it as probably the greatest breakthrough in engineering history. Unfortunately they can't. Neither can the medics and biologists model how the brain works to create intelligence and consciousness. The fact is, something astonishing happens in Maria's head that still defies description by our brightest minds. 

When that wonderful day comes - when scientists find a way to counter the effect of the CREBBP or EP300 mutation - chances are they won't know how it works on the brain. Nevertheless, I'll be one of the first to praise the wonders of science, even though we might be none-the-wiser about the nature of intelligence.