DiGeorge syndrome (22q11 deletion)
DiGeorge syndrome was discovered by Dr Angelo Digeorge in the mid 1960's.
DiGeorge syndrome is a genetic disorder that's usually noticeable at birth. Children with the condition can have heart defects, learning difficulties, a cleft palate and potentially many other problems.
In almost all cases, these symptoms and features result from a missing piece of chromosome – a genetic fault, or mutation, called 22q11 deletion.
This genetic fault can potentially cause many different combinations of symptoms (syndromes), of which DiGeorge syndrome is just one. The 22q11 deletion is estimated to affect at least one in every 4,000 births.
DiGeorge syndrome is generally considered one of the most serious types of 22q11 deletion, but each child with it is affected differently and the symptoms can vary widely. Not every child is severely affected and many will grow up to have a normal life expectancy.
What are the main features of DiGeorge syndrome?
DiGeorge syndrome can potentially cause many different problems affecting various areas of the body.
The main features are described below, but bear in mind that the severity of these problems varies from child to child and some children with the syndrome will only experience a few of them.
Most children with DiGeorge syndrome have heart abnormalities from birth, such as a hole in the heart or a problem with the main artery leaving the heart (the aorta).
Many children will have four specific structural abnormalities of the heart, collectively known as 'tetralogy of Fallot'. These are:
pulmonary stenosis – narrowing between the right heart chamber and the main blood vessel (pulmonary artery) that carries blood from the heart to the lungs
ventricular septal defect – a hole between the right and left pumping chambers (ventricles) of the heart
over-riding aorta – the entrance to the aorta is next to the ventricular septal defect, allowing low-oxygen blood to flow through it
thick right ventricle – the heart has to work harder to pump blood through the narrowed pulmonary artery, causing the muscle to thicken
A doctor will carry out an echocardiogram (ultrasound of the heart) to check if your child has these heart problems. Surgery may be needed to correct some of them.
Read more about congenital heart disease.
Commonly, children with DiGeorge syndrome will have slow development of speech and poor concentration, and may struggle with maths and problem solving as they grow up.
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder are fairly common, which can make learning even more difficult.
The earlier any learning difficulties are noticed the better, as prompt treatment can reduce their impact and allow parents and teachers to organise any special help needed at nursery or school.
Problems with the mouth, feeding and hearing
Some children with DiGeorge syndrome have a cleft palate (hole in the roof of their mouth) and many more will have a problem with the surrounding mouth muscles. A few will also have a cleft lip (split in the upper lip). Read more about cleft lips and palates.
These problems can result in:
difficulty with speech and language and a "nasal" voice
feeding problems – they may find it hard to chew and swallow solids (dysphagia), may occasionally regurgitate food through their nose when swallowing, and typically do not put on much weight
ear infections such as glue ear, which may lead to temporary hearing loss.
Children with DiGeorge syndrome tend to have the following features:
a long, narrow face
wide-set, almond-shaped eyes
a broad nasal bridge and bulbous nose tip
a small mouth
small, low-set ears that are folded over at the top
a cleft lip
a cleft palate
an irregular skull shape (craniosynostosis)
Many of these features will become easier to spot as the child gets older.
Children with DiGeorge syndrome generally have weak immune systems because of a problem with the thymus gland – a gland in the chest that produces cells needed to fight invading germs. It means they may be susceptible to recurrent infections such as oral thrush and pneumonia.
However, immune system problems often improve with age and routine childhood vaccinations should normally be given to prevent several serious infections.
Hormone and growth problems
Many children with DiGeorge syndrome also have an underactive parathyroid gland, known as hypoparathyroidism.
There are four tiny parathyroid glands, each the size of a grain of rice, in the neck behind the thyroid gland. They produce parathyroid hormone to help control the levels of calcium, phosphorus and vitamin D in the bones and blood.
An underactive gland causes low levels of calcium in the blood, which can cause problems such as tremors and seizures (fits), although these are unusual after infancy. Calcium supplements may be given to treat this.
Some children may also be short for their age because of a growth hormone deficiency, and they may have an underactive thyroid gland.
Emotional and mental health problems
Children with DiGeorge syndrome may find it difficult to make friends with children their own age and may avoid making eye contact.
They may have rapid mood swings, swinging from quietness to hyperactivity, and have unexpected temper tantrums.
Teenagers and adults with DiGeorge syndrome are more likely to develop depression and other psychiatric conditions, including schizophrenia.
Bone and muscle problems
Bone and muscle problems are fairly common in people with DiGeorge syndrome.
Problems that can occur include:
reduced muscle tone or "floppiness" (hypotonia)
abnormalities of the spine, such as a curved spine (scoliosis)
clumsy walking or hand movements
recurrent leg pains
weak muscles, resulting in hernias and constipation (as the gut muscles don't work very well)
a high shoulder blade
over-flexible joints (joint hypermobility)
Possible eye problems include a squint (where the eyes point in different directions), a hole in the iris of the eye known as coloboma, and childhood cataracts – although these won't always need treating.
It's quite common for a child with DiGeorge syndrome to have a missing kidney, or for one kidney to be smaller than the other. An ultrasound scan will pick this up.
This shouldn't cause any problems and no treatment is necessary.
What is 22q11 deletion?
Chromosomes are X-shaped strands of genes, which provide instructions for a person's characteristics. Most people have 23 pairs of chromosomes – one of each pair from their mother, and the other from their father.
Each chromosome has a long arm (referred to as 'q') and a short arm ('p'). In 22q11 deletion, a tiny part of the long arm of chromosome 22 is missing (at position 11).
22q11 is responsible for a wide range of syndromes and conditions, ranging from mild to severe. DiGeorge syndrome is at the more severe end of the range. Scientists are not sure why the same missing piece of chromosome can result in different genetic syndromes.
How does the mutation happen?
In most cases of DiGeorge syndrome, the missing piece of chromosome would already have been missing from the egg or sperm from which the baby was conceived. This can happen by chance when DNA is copied to make sperm and eggs and it can't be predicted or prevented.
In these cases, there is usually no family history of the condition.
In around 10% of cases, the 22q11 deletion will have been passed on to the child by one of the parents who has the mutation themselves.
How is DiGeorge syndrome diagnosed?
The piece of missing chromosome that causes DiGeorge syndrome is so small that it cannot be seen under a microscope. Instead, a special test called the FISH test (fluorescence in situ hybridisation) will be needed to diagnose the condition.
This test shows whether the region of chromosome 22 is present. If only one copy of chromosome 22 'lights up' with fluorescent DNA dye, rather than both copies, the test is positive for 22q11 deletion.
The FISH test can be carried out to diagnose an unborn baby using a sample of cells from the placenta (chorionic villus sampling) or a sample of fluid surrounding the baby (amniocentesis). It can be carried out using a blood sample in children and adults.
However, this test doesn't pick up every case of DiGeorge syndrome. Some people will need to have more advanced DNA tests and occasionally the diagnosis may be solely made on the characteristic features and symptoms.
What are the chances of my next child having it?
A parent with DiGeorge syndrome has a 50% chance of passing on the condition to their child. This applies in each pregnancy. If neither parent has the condition, the risk of having another child with it is around 1%.
If you're at risk of having a baby with DiGeorge syndrome, you should be referred for genetic counselling to discuss the level of risk and what your options are.
The earliest an unborn baby can be tested in pregnancy is at 10-12 weeks, by chorionic villus sampling. Testing is also available by amniocentesis from 15-16 weeks onwards.
It's important to be aware, however, that these tests cannot predict how severely a child with 22q11 deletion will be affected.
Find out more about genetic testing and counselling.
What help and support is available?
There's no cure for DiGeorge syndrome, but many of the problems experienced by people with the condition can be monitored and treated if necessary.
Your child will have regular tests from infancy onwards, including:
hearing tests and eye examinations
blood tests to check hormone and calcium levels
medical tests of their immune system
kidney and heart scans and tests
Before they start school, your child's developmental progress and speech and language development should be carefully assessed. If your child has a learning disability, their educational needs can be met either in a mainstream school with extra support, or in a special school. Read more about education for children with learning disabilities.
A physiotherapist can help with any physical problems – for example, shoe inserts (orthoses) may help your child's leg pains. Read more about physiotherapy.
Speech therapy can help with speech problems, and dietary changes or tube feeding may be needed temporarily to help with swallowing or feeding difficulties.
Surgery may be needed to correct any severe problems, such as heart surgery or an operation to reduce the amount of air escaping through their nose (if your child's speech is very nasal).
You may find it useful to discuss your concerns with a social worker, psychologist or counsellor, who you can contact directly or via your doctor. Read more about caring for a disabled child and childcare options for disabled children.
What is the outlook?
Nowadays, most children with DiGeorge syndrome will survive into adulthood – particularly if heart problems are detected and treated early on. Less than 5% of babies die before their first birthday.
As a child with DiGeorge syndrome gets older, physical features such as heart and speech problems tend to become less of an issue, but behavioural, learning and mental health problems may affect daily life.
Many of those who reach adulthood will have a relatively normal life span, although for some people, ongoing health problems mean their life expectancy is lower than the average. Regular check-ups are necessary to monitor the condition.
Adults with DiGeorge syndrome are often able to live independently and have jobs, although some people experience social isolation and employment problems as a result of their condition.