What's in a name

There is a poem "The Blind Men and the Elephant' by John Godfrey Saxe (1816-1887) which is based on a parable which originated in the Indian sub-continent. The story is about six blind men who come across an elephant. In turn each man touches a part of the animal and describes what the animal is like. The first touches the side of the elephant and says it is like a wall, the second a tusk which is described as a spear, the third holds the trunk which he describes as a snake, the fourth grabs a knee which he says is like a tree, whilst the fifth grabs an ear which is says is like a fan. Finally the last man hold the elephant's tail which he explains is like a rope.  Each man is correct in his description but none of them is able to visualise the whole picture.

I first came across this story a few years ago when it was used at a conference I attended to describe how knowledge of the condition I am referring to as 22q 11.2 DS has developed over the years.

History of the condition

I suspect the condition has been around for centuries but as around 75% of cases have heart defects, before the advances in heart surgery over the past 30 years or so many people would not have survived beyond infancy.

The following information is taken from "Educating Children with Velo-Cardio-Facial Syndrome" by Donna Cutler-Landsman and more specifically from a chapter written by Robert J. Shprintzen PhD who first used the term Velo-Cardio-Facial Syndrome in 1978.  I hope this is an accurate summary and apologise to Dr. Shprintzen if I have got this wrong.

The first medical report which described a combination of some of the the anomalies associated with the condition appeared in a paper by Sedlaakova in 1955. The articles was in a medical journal published in the former Czechoslovakia and as these were the days of the Cold War the publication was not seen outside of Eastern Europe.

By 1968 an American doctor the late Italian-American doctor Angelo DiGeorge had identified a number of anomalies which occurred together including an under active parathyroid gland, resulting in low calcium levels, underdeveloped or absent thymus, resulting in problems with the immune system and heart defects (e.g. tetralogy of Fallot, interrupted aortic arch, ventricular septal defects). This combination came to be known as "Di George Syndrome".

Around 1976 papers started to be published in Japan describing a similar combination of anomalies under the name of Conotruncal Anomalies Face Syndrome.

While as mentioned above in 1978 Dr. Shprintzen and his team were coining the phrase Velo-Cardio-Facial Syndrome (VCFS) (sometimes referred to as Shprintzen syndrome) to described a group of patients with a similar combination of anomalies including cleft lip and/or palate, heart defects, absent or small thymus, and in some, but not all, cases low calcium levels.

In 1985 Dr. Shprintzen's group had determined that Di George was actually a sequence (a series of conditions that do not have a common cause) rather than a syndrome (a series of conditions with a common cause). This is because Di George Sequence can also be found in people with several other genetic conditions including Down's syndrome.

By1992 Dr. Peter Scambler was studying children with Di George Sequence and noticed that some but not all had a piece of DNA missing from Chromosome 22 and wondered whether the same was also true of patients with VCFS. A number of blood samples of people with VCFS but without the under active parathyroid gland associated with Di George Sequence were sent to Dr. Scambler.  When tested all of the samples showed the 22q 11.2 deletion.

So in summary.  

i) We have Di George Syndrome which is really Di George Sequence,
ii) Only some of the people with Di George Syndrome / Sequence have the 22q 11.2 deletion,
iii) VCFS is the same as 22q 11.2 DS, and
iv) the syndrome has at various times also been called Shprintzen syndrome, Sedlackova syndrome, and conotruncal anomaly face syndrome.

Confused ?? No wonder the condition remains relatively unknown.

However there now appears to be some momentum towards a common name and I would hope that social media campaigns like #22qAwarenessDays will bring knowledge of the condition to a wider audience.

Striped Socks

Sarah continued her recovery at home and was making good progress. In fact life was pretty much back to normal. Within weeks she was no longer on medication and was again putting on weight. There was however one thing playing on my mind. When Sarah was first admitted to Guy's we had been told the hospital wanted to do a test to check for any genetic conditions. I knew that a sample had been taken but did not recall ever seeing the results.  I told myself, without conviction, that as we had not heard anything from the hospital the result must have been negative.  In January 2006, three months after Sarah's surgery, we had our first check up at the local cardiac clinic and received the good news that Dr. Bell, Cardiology Consultant, was please with her progress. I took the opportunity to ask about the result of the test and was told they could not find the results on file but would check. The following day we received the call I had half expected. The test had revealed a genetic abnormality and an appointment would be arranged with the genetics team at Guy's.

As I sat in the waiting room for the Genetics Clinic at Guy's Hospital I noticed that there were 23 photographs on the wall and that each photograph was of a pairs of striped socks of varying sizes and colours. At first glance this looked like a strange piece of artwork for a waiting room but when reading the accompanying explanation its all made sense.

The 23 photographs represent the 23 pairs of chromosomes in a normal human cell.  At conception we get one set of 23 chromosomes from our mother and one set of 23 chromosomes from our father. We have 22 pairs of Chromosomes numbered 1 through 22 and two sex chromosomes.  We always receive an X sex chromosome from our mother with either and X or a Y sex chromosome from our father.  X from Mum and X from Dad and the result is a baby girl. X from Mum and Y from Dad and the result is a boy.  Sometimes a baby acquires an extra chromosome ending up with 47 instead of 46. the most common example of this is Down's Syndrome where a person has an extra copy of Chromosome 21.

When viewed under a microscope a chromosome looks like it has a number of horizontally striped bands hence the stripes on the socks.

The geneticist told us that Sarah has 22q11.2 is deletion syndrome which means that she has a small piece of genetic material missing on one copy of Chromosome 22. The deletion occurs on the long arm of the Chromosome (q) at band 11.2.  The amount of genetic material missing is typically around 40 genes.  Although every one with 22q11.2 DS has the same part of Chromosome 22 missing no two cases are the same.  A full set of chromosomes can be viewed as a blueprint for the body creating how the foetus develops and how we develop and grow after birth.  If part of the blueprint is missing then a number of errors are likely to occur.  Around 180 anomalies are caused by this deletion and a list of this can be found at http://www.22crew.org/professionals/velo-cardio-facial-syndrome-specialist-fact-sheet .

Typically a person with 22q will experience around 30 of these anomalies throughout their life. In my mind this condition is a bit of an "unlucky dip". Nature take out a handful of genes and depending on the genes removed the level of symptoms can be mild or severe.

The frequency of 22q is believed to be around 1 in 1800 live births. This compares with an incidence of 1 in 1,000 for Down's syndrome which is the most common genetic disorder.

The22 Crew www.22crew.org a charity and support group of which I am a trustee is currently hoping to fund a project to confirm the incidence of this condition.

www.22crew.org

Old Hospital - New Hospital

Congenital heart disease is one of the most common types of birth defect and in the UK it is estimated to affect around 9 in every 1,000 births or slightly just under 1%.
(Source: http://www.nhs.uk/conditions/Congenital-heart-disease/Pages/Introduction.aspx).

However it is estimated 75% of people with 22q11.2 DS have some form of congenital heart defect and the majority of cases of 22q are diagnosed by paediatric cardiologists.  Cardiac conditions associated with 22q 11.2DS include

VSD (ventricular septal defect)
ASD (atrial septal defect)
Pulmonic atresia or stenosis
Tetralogy of Fallot
Right sided aorta
Truncus arteriosus
PDA (patent ductus arteriosus)
Interrupted aortic arch, type B
Coarctation of the aorta

Further information on these conditions can be found on the website of The Children's Heart Federation
http://www.chfed.org.uk/how-we-help/information-service/heart-conditions/

The severity of these conditions varies greatly and in many respects Sarah was "fortunate" to have an interrupted aortic arch rather than one of the other conditions. As Mr. Austin said at the time all of the plumbing was in place it it just needed to be connected properly. Sadly many other conditions are more complex requiring multiple surgical procedures and unfortunately in some cases although medical knowledge continues to advance currently the condition cannot be treated.

Back to October 2005 and Sarah continued to recover from her surgery, the mood on the ward was fairly relaxed as, where possible, patients were being discharged as the cardiac unit geared up for the its move to the new Evelina Children's Hospital the first new children's hospital built in London in 100 years.

The modern Evelina Children's Hospital

The original Evelina Children's Hospital was founded in 1869 by Baron Ferdinand de Rothschild, in memory of his wife, Evelina who died in childbirth. The original plan was for a maternity hospital but he was persuaded to fund a hospital serving the poor children of South London.  Following the introduction of the NHS, the hospital became a department of Guy's and effectively ceased to exist when services were moved into Guy's Tower in the mid 1970's becoming little more than the name of the children's ward. The hospital was reborn in 2005 with the construction of the new hospital on the site of the former nurses' home at St. Thomas's Hospital.  The hospital is designed around children and in the ground floor waiting area there is a large blue helter-skelter. Now if the hospital was a commercial company I would say that it had be designed to generate new business as having seen how fast children come down the slide I am convinced that it must have delivered a significant number of new "customers" for St. Thomas's Accident & Emergency department !

The day of the move arrived and Sarah and Colleen were in the convey of ambulances making the short journey to the new site. A journalist and photographer from The Times weekend supplement were on hand taking pictures of all the patients. For several weeks we eagerly awaited the Saturday edition of The Times to see if there was an article. The article duly appeared but Sarah did not, typical of the media's obsession with youth there was a younger patient barely two weeks old who stole the limelight !!

One feature of the wards is that built in to the wall beside each bed is a pull down bed which can be used by a parent wishing to stay the night with their child. This is a different world to the one I experienced when I was a child.

I was born with a cleft lip and had surgery at 6 months. By the time I was about four and half a second operation required and I was taken by my parents the the Queen Elizabeth Hospital in Hackney. I was put in an ambulance with several other children and babies and we waved goodbye to our parents as we were transported 20 mile across London to Banstead in Surrey. I think I must have been in hospital for at least a week and was visited once when my parents took the special coach service that ran to the hospital on a Sunday.  This was the latter part of the 1960's when cars and telephones were luxury items and a call to the ward to enquire about my condition would have involved either a walk to the local phone box or finding a neighbour willing to let my parents use their phone in return for a threepenny bit !!

Threepenny bit for the benefit of younger readers

I am not sure if I was traumatised by this event but two things stick in my mind. The first was being put in a bath as soon as I arrived at the hospital. In the 1960's no-one was allowed near a ward until they had been doused in eau de carbolic and secondly being told by a teacher that I could not participate in the hospital school as I was too young.

Fortunately things have moved on in the last 50 years particularly in the world of medical treatment and just 7 days after undergoing surgery Sarah was discharged from hospital and we were on our way home.

The size of a walnut

The news that Dr. Hobbins had detected a heart murmur was a bit of a surprise but there was no obvious sign of a heart problem and I was fairly optimistic that it would turn out to be a false alarm so the following day I went off to work as normal.
At around 11a.m I received a call from Colleen which confirmed my optimism had been misplaced. The echocardiogram had shown an anomaly and Sarah's doctor was on the phone to the specialist cardiac team at Guy's Hospital.  At that point I was unable to concentrate on anything and sat there waiting for more news. Around half an hour later I received a call from my sister-in-law telling me that Sarah and Colleen were in an ambulance on the way to Guy's.

In 2005 I was working in central London close to Tower Bridge and as soon as I received the call I was on my way to Guy's Hospital which was a brisk 15 minutes walk away.

Dr. Owen Miller, consultant in paediatric and fetal cardiology, performed another echocardiogram and gave us the diagnosis that Sarah had an interrupted aortic arch (IAA) and a large ventricular septal defect (VSD) which is more commonly know as a hole in the heart. She was experiencing heart failure and surgery was the only option. It was also mentioned that as many congenital heart defects are caused by genetic conditions it was advisable to do a blood test.

Around 50% of all babies with this type of IAA and VSD have 22q11.2 DS.

At that point there was little we could do but wait and contemplate the fact that our 17 week old baby was about to undergo major surgery. Around 48 hours after Sarah had been admitted to Guy's the medical team were discussing whether or or not to proceed with the operation as they thought Sarah may have had an infection which could cause complications. That afternoon we received the news the operation was going to take place the following morning.  I must admit we had mixed feelings as on the one hand we wanted the problem fixed as soon as possible but on the other we were apprehensive about the forthcoming surgery.

That evening we met Mr. Conal Austin the surgeon who was to perform the operation. He described in detail how he would undertake the repair and helped to ease the anxiety we were feeling at that time.

As a general rule of thumb the size of a person's heart is about the size of a fist. In the case of a 17 week old baby the heart is about the size of a walnut. I still find it unbelievable that life saving surgery can be successfully carried out on such a small object and we are very privileged in this country to have surgeons with the knowledge and skill to perform such intricate surgery.

After listening to what was about to take place I was asked to sign the consent form which included the potential risks associated with surgery of this nature including the 5% risk of death during the operation.

When thinking about risk human nature is to focus on the downside. However in such a situation my recommendation is to look at the risk equation from the other side and I told myself instead of a 5% risk of death look at it as a 95% chance of surviving which sounds much better.

Thursday 13th October  (Luckily I am not superstitious)

Sarah was scheduled to be the first operation of the day but due to an administrative mix up another patient went down to theatre first. This not only prolonged the agony for us but Sarah had not been fed since the previous night and was becoming quite agitated. At about 11a.m. we got the call to go, carrying Sarah down to theatre, and leaving her in the care of the surgical team was probably the worst thing I have ever had to do and the memory of this will live with me for ever.

The next few hours were the longest I have experienced, we took a walk along the South Bank and went for lunch but had little appetite.

Fortunately we had been offered a room at the local Ronald McDonald House which provides accommodation for families of seriously ill children and went back to the room to rest and wait. Around 3.30 p.m. we got the call to say Sarah was on her way to intensive care and we rushed back to the hospital to see her.  Although she was covered in tubes, drips and drains she had come through the surgery and Mr. Austin told us that the operation had gone well.

The body's powers of recovery are amazing and hour by hour we could see an improvement. Often we would go out to get something to eat or drink and when we got back to intensive care we found that another tube, drain or monitor had been removed.

Barely two days later we were back on a normal ward feeling confident that the worst was over.

The Phoney War

For as long as I can remember I have always been interested in history, eagerly devouring books, magazine articles and TV documentaries. The next part of my 22q story resembles a period of the Second World War which in Britain is referred to as "The Phoney War" covering the period from the initial declaration of war in September 1939 when thousands of children, including my late father, were evacuated from major cities until April 1940 when Denmark and Norway were invaded. A period marked by limited military activity in Western Europe.

Colleen's pregnancy continued without incident, she had a couple of scans and nothing untoward was detected. Colleen was keen to know the sex of our baby but successfully keep the news from me as I preferred to wait until the big day.

The due date came and went and twelve days later at around 3 a.m. Colleen went into labour and we set off on the short journey to the local hospital. Labour was progressing nicely during the morning and early afternoon but by early evening progress had slowed and the baby was showing some signs of stress.

The medical team took Colleen into theatre and I was directed to the room where the medical scrubs were kept and told to get kitted out. So there I was, someone who had always been squeamish about the sight of blood, needles and anything medical, dressed up ready to go into an Operating Theatre.
To my immense surprise I stayed upright and didn't pass out there and then !!

On my way to theatre I stopped off to collect a nappy and babygrow from the bag we had taken to the hospital. I unzipped the bag and my eyes were immediately struck by an explosion of pink. The secret was out we were having a baby girl !

In theatre there was an initial sense of panic although this quickly subsided and the team got to work on delivering the baby by caesarean section. I had always thought new born babies cried the minute they arrived and was therefore concerned when a saw a limp silent Sarah being passed to another doctor. The silence seemed to last for ages but in reality was probably less than a minute. I then heard the doctor say "I have a strong heartbeat" followed shortly afterwards by Sarah's first cry. I felt an immediate sense of relief as Sarah was whisked off to Special Care Baby Unit where she stayed for several days receiving antibiotics as there was concern that she had ingested meconium.

After 6 days Colleen and Sarah left hospital and we could start being a family. The initial excitement had passed and we quickly got into the routine of feeds and nappy changes. I am please to say I very quickly developed the knack of sleeping through the night undisturbed by night feeds !   Sarah was a very good baby and cried very little. Her cries were more like little squeaks which resulted in us giving her the nickname "Squeaky" which we still use today.

Sarah fed well, slept well and continued to put on weight. The only unusual thing was when she brought up her milk she was sick thought her nose as well as her mouth. The weeks passed uneventfully and we even had time to spend a relaxing week on holiday in the Cotswolds.

Chipping Campden, Gloucestershire where we spent a relaxing week

Around three and a half months later we were at a family christening and Sarah was very restless, unable to sleep and constantly wanting to be carried. For the first time we noticed a reluctance to feed and our GP referred her to the local hospital. The hospital diagnosed bronchiolitis and Sarah was admitted. Several days later Sarah was still in hospital and although she was not getting better she did not appear to be getting worse. Imagine our surprise when following an examination by a senior paediatrician we were given the news that she had noticed a slight heart murmur, we were told that it was probably nothing to worry about and as a precaution she would undertake an echocardiogram the following morning.

Like the people of Britain in Spring 1940 who I mentioned at the start of this piece we were just about to experience our first bombshell.

The First Scan

Do you know what 22q 11.2 Deletion Syndrome is ?

If you had asked me this question nine years ago I would not have known the answer. Was it some kind of chemical formula or part of a mathematical equation ? To be honest nine years ago did I really care ?

In spring 2005 my wife Colleen and I were more focused on the arrival of our baby. We had got married the previous year and not being the youngest of newlyweds had decided to start a family straight away. With the biological clock ticking the big concern was the risk of Down's Syndrome which as everyone knows is more common where older parents are concerned.

So early in Colleen's pregnancy we went off to King's College Hospital for a nuchal translucency scan which measures by ultrasound the fluid at the back of the neck of the foetus. This measurement is then used to predict the risk of Down's Syndrome.

We were told the risk was within the normal range and the scan was OK.

Like all prospective parents we were hoping for a healthy baby. Having had the nuchal translucency scan we had ticked the box for Down's Syndrome, so no need to worry about a chromosome abnormality!!

King's College Hospital, London

Welcome !!

Inspired by my friend Mike Woods who writes an excellent blog http://rulesfoolsandwisemen.blogspot.co.uk/ I have been thinking of writing my own blog for some time.

To date, despite my best intentions, I have so far not managed to get round to it.

Now I have no excuse.

22q Awareness Days is a campaign which aims to enhance the general public knowledge of the genetic condition 22q11.2 Deletion Syndrome over a period of 22 consecutive days from 27th April 2014.

https://twitter.com/search?src=typd&q=%2322qAwarenessDays  https://www.facebook.com/22qAwarenessDays

22q11.2DS is believed to be the second most common genetic condition after Down's Syndrome.

Most people know something of Down's Syndrome but very few have ever heard of 22q11.2 DS.

This is a condition which affects my daughter Sarah and I thought it would be a good idea to share my family's experience of 22q11.2DS and hopefully bring knowledge of this condition to a wider audience.

My objective is to write a post each day for the next 22 days and I hope you will join me on this journey.