22q11 Deletions: DiGeorge syndrome (DGS); velo-cardio-facial syndrome (VCFS); Shprintzen syndrome; CATCH 22

The chromosome 22q11 deletion is found in a wide variety of apparently unrelated conditions. The deletion was first recognized in 1981 in Di George syndrome, affecting the heart, calcium and resistance to infection and occasionally the palate. Velo-cardio-facial syndrome (VCFS) with disorders in structure and function of the palate, heart defect and a facial appearance with features similar to each other, also known as Shprintzen syndrome, was considered a quite separate condition until the genetic basis was found to be the same as Di George in 1988. In Japan it was called conotruncal anomaly face syndrome. It has also been called CATCH 22, after some of the most important medical features (C=cleft palate, A=appearance, T=thymus/immunology deficiency, C=calcium salt low, H=heart defect), but this name is not favoured when describing people.

The effects can be seen as a range of severity from mild to moderate in VCFS, to more severe in Di George syndrome.

The main features found in the 22q11 deletion are numerous and affect every body system but the severity varies from person to person with two people from the same family not necessarily showing the same features to the same extent. These features include:

Heart problems (see entry, Heart Defects) which affect about seventy-five per cent of people with 22q11 deletion. The most common heart problems are: tetralogy of Fallot (a combination of four heart defects), interrupted aortic arch (failure of development of a section of the main artery supplying the body), ventricular septal defect (hole in the ventricle of the heart which allows blood to flow where it should not) and right aortic arch (instead of the usual left side).

Learning disabilities (see entry, Learning Difficulties) affect about sixty-five per cent people with 22q11 deletion and include: slow development of speech and language; poor concentration; and an inability to reach age appropriate milestones. The child may have difficulty at school with arithmetic, comprehension and problem solving, but may be particularly good at learning by rote and reading. The learning difficulties may be associated with a smaller than usual head size or rarely, by craniosynostosis (where the bones in the skull close before they should). ADHD - Attention Deficit Hyperactivity Disorder is more common than usual, making learning difficult, and may not respond to the usually recommended medicines. Early intervention can help reduce the problems.

Cleft palate (see entry, Cleft Lip and/or Palate) and velopharyngeal insufficiency are found in around sixty per cent of people with 22q11 deletion. The palate (or roof of the mouth) closes off the nose from the back of the mouth during speech and can contribute to a delay in speech and language. Regurgitation through the nose during swallowing can also occur, although it is not very common. This effect on speech and swallowing is called velopharyngeal insufficiency (VPI). Problems that might occur include a cleft palate (where there is a hole in the palate) or a submucous cleft (where the roof of the mouth may look fine, but the muscles are not in the right position). Another problem which may be present is weakness and in-coordination of the muscles in the roof of the mouth. VPI also occurs in some patients because the adenoids are poorly developed or the base of the skull is shortened. VPI results in an excessively nasal sounding voice, and makes consonant sounds more difficult.

Speech problems (see entry, Speech and Language Impairment) are common with clefts or VPI but may also result from developmental delay, learning difficulties, or hearing difficulties which are caused by problems with the Eustachian tubes (which drain fluid from the ear). This can cause glue ear, middle ear infections which are made worse or more frequent than usual due to the immune deficiency, developmental delay or learning difficulties.

Feeding difficulties are common in infancy and early childhood because of the combination of cleft palate and/or VPI, and regurgitation of stomach contents into the gullet and mouth (gastro-oesophageal reflux). There may also be problems with chewing and swallowing solids (dysphagia) which may benefit from specialist help.

People with 22q11 deletion tend to have similar facial features including almond shaped eyes, elongated facial features often with flat cheek bones, a long, 'strong' nose with a relatively broad and prominent nasal bridge, small nostrils, and small jaw. The ears may be small, prominent, and folded over at the top. The fingers are thin, and tapering at the ends with small underdeveloped nails. These features become easier to identify as the child grows older.

As some degree of thymus or T-cell malfunction is frequent, children often have infections due to impaired immunity but it is unusual for it to fail completely, and any immune problems often improve with age.

The parathyroid glands in the neck may be underactive which causes low levels of calcium in the blood, called hypocalcaemia, and this may cause convulsions. These are unusual after infancy, even if the hypocalcaemia persists. Hypothyroidism (underactive thyroid) (see entry, Thyroid Disorders) and growth hormone deficiency occurs occasionally. As individuals with 22q11 are generally among the smallest ten per cent, their growth should be monitored. Any slowing of growth may need to be checked in case of nutritional and hormone deficiencies.

Emotional responses may be immature so some children may have difficulty in making relationships with children of their own age, or sometimes they may avoid eye contact. Extremes of rapid mood swings or behaviour varying from quiet inactivity to hyperactivity, and unexpected temper outbursts may cause serious management difficulties. After childhood, depression and other psychiatric conditions, including schizophrenia, have been found to be somewhat commoner than in the general population.

Kidney problems (see entry, Kidney disease) are found in thirty-five per cent of people with 22q11 deletion. It is quite common for a kidney to be absent, or for one kidney to be smaller than the other although its condition generally doesn't get worse. However, even if a child does not seem to have a kidney problem, an ultrasound examination should be made to confirm this.

Bone and muscle problems are more common in people with 22q11 deletion than usual. Problems that can occur include: scoliosis (curvature of the spine), Sprengel's shoulder (where the shoulder blade is in a higher position than normal), talipes (club foot) (see entry, Lower Limb Abnormalities) and rheumatoid arthritis (see entry, Arthritis (Juvenile Idiopathic)).

Muscle tone is often reduced. A lack of muscle bulk is common, so the children appear to have a small build. Joints that can be extended more than usual (hypermobility) may result in complaints of leg pains on walking and exercise. Hernias occur due to muscle weakness. Constipation is more common as the gut muscles don't work so well. Testicles may not descend at the normal age.

Eye abnormalities include coloboma (deficiency in a local spot of the eyeball's layers), some developmental differences from usual and small cataracts which are unlikely to need intervention.

Rarely, a laryngeal web may cause breathing difficulties from birth.

Inheritance patterns
In 22q11 Deletion syndromes, each chromosome has a long (q) and short (p) arm. In this syndrome a tiny part is missing (deleted) from the long arm (q) of one of the two chromosomes 22's at position 11 on that chromosome. In very few individuals it is not possible to show this chromosome deletion even though they undoubtedly have the condition.

In many affected children the deletion has started in the particular egg or sperm which went to form them, just by chance when the chromosomes were being copied to pass on, but in a small number (ten per cent) one parent has it and has passed it on. The deletion is shown by the FISH (fluorescence in-situ hybridisation) test, when instead of both chromosome 22's 'lighting up' with a special fluorescent DNA tag only one does. If a parent carries the 22q11 deletion, the inheritance mode is autosomal dominant. When neither parent shows the deletion there is still a one to two per cent risk of another affected child as it may only be carried in the germinal cells of the parents ovaries or testes.

22q11 deletion occurs in around 1 in 4,000 of the population. The very variable ways it affects individuals can result in a lengthy time to obtain a diagnosis.

Prenatal diagnosis
Amniocentesis or Chorionic villus sampling will detect the chromosome 22 deletion. Ultrasound scans can detect most heart defects.

Medical text written August 2003 by Dr A Habel, Consultant Paediatrician, Great Ormond Street Hospital, London, UK.

Further Online Resources
Medical texts in The Contact a Family Directory are designed to give a short, clear description of specific conditions and rare disorders. More extensive information on this condition can be found on a range of reliable, validated web sites and links to them are included in the CD-ROM version of this Directory. Further information on these resources can be found in our Medical Information on the Internet article.

Max Appeal
Lansdowne House
15 Meriden Avenue
Stourbridge
DY8 4QN
Tel: 0800 389 1049 Freephone Helpline
Tel: 01384 821227
e-mail: info@maxappeal.org.uk
Web: http://www.maxappeal.org.uk

The Appeal is a National Registered Charity No. 1088432, established in 1999. It provides support for all forms of 22q11 deletions including DiGeorge syndrome, Velo-Cardio-Facial syndrome, Shprintzen syndrome and the 22q11 form of Opitz G/BBB syndrome. It offers contact with other families and has regional groups. It is developing international and research links. It publishes a quarterly newsletter and has a wide range of information available, details on request. The Appeal has over 470 members.

Group details last updated May 2007.