/
/

22q11 deletion syndrome

This is part of Rare diseases.

Diagnosis: 22q11 deletion syndrome

Synonyms: DiGeorge syndrome, Velocardiofacial syndrome, VCFS, CATCH 22

Innehåll


Date of publication: 2014-03-24
Version: 3.0

ICD 10 code

D82.1

The disease

22q11 deletion syndrome can affect many organs in the body. A number of congenital defects may occur such as heart defects, cleft palate, and underdeveloped thymus and parathyroid glands. Common symptoms are feeding difficulties, speech and language problems, frequent infections of the respiratory tract, learning difficulties, and neuropsychiatric abnormalities such as attention disorder and problems with social interaction. Teeth, hearing, vision, and growth may also be affected. The severity of the various symptoms ranges from very mild to severe.

22q11 deletion syndrome is the current name of the condition, and best describes its cause. It is also known as velocardiofacial syndrome (VCFS), DiGeorge syndrome and, previously, as CATCH 22.

DiGeorge syndrome was first described in 1965 by paediatrician Angelo DiGeorge from Philadelphia. The characteristics of the syndrome included the absence of the thymus, low blood calcium levels owing to impaired functioning of the parathyroid glands, heart defects and a characteristic appearance. The syndrome was divided into two types, complete DiGeorge syndrome characterised by a severe immunodeficiency, and partial diGeorge syndrome associated with mild to moderate immunodeficiency. Currently the name DiGeorge syndrome is used primarily in rare instances of severe immunodeficiency.

In 1978, Robert Shprintzen, a New York speech pathologist, described a syndrome in which palate function was impaired and the palate itself was sometimes cleft. This syndrome was characterised by speech abnormalities such as hypernasal speech, learning difficulties, a characteristic facial appearance and, frequently, by congenital heart defects. Shprintzen named this syndrome velocardiofacial syndrome (velo = roof of the mouth, cardio = heart, facial = of the face).

In the early 1990s, it was found that one and the same chromosomal aberration caused both syndromes and an English research team suggested the name CATCH 22. This is an acronym in which C stands for Cardiac anomaly, A for Anomalous face (the characteristic appearance), T for Thymic hypoplasia (underdeveloped thymus gland), C for Cleft palate, H for Hypocalcaemia (low blood calcium level), and 22 for chromosome number 22.

Occurrence

Approximately 25 children in 100,000 are born with 22q11 deletion syndrome. To date (2013) approximately 300 to 400 people have received the diagnosis in Sweden. Since recognition of the syndrome is relatively recent and many individuals have only mild symptoms, there is reason to believe that there are many undiagnosed cases.

Cause

The syndrome is caused by a deletion of a small piece of the long arm (q) of one of the chromosomes in the twenty-second chromosome pair (22q11.2). This means that a small part of the genetic material from this region is missing, and hence that normal function of these genes is affected.

Many research groups have tried to identify which genes and genetic mechanisms cause the characteristic symptoms of the disorder. Several researchers have shown that one of the approximately 60 absent genes, the TBX1 gene, can explain certain symptoms and abnormalities associated with the syndrome. The TBX1 gene controls the formation of (codes for) the Tbox1 protein which is important for the formation of certain tissues and organs, including the heart and thymus. However, this does not provide a complete answer, and more information about the deleted genes and their mechanisms remains to be discovered. Other genes, or some form of interplay between genes, may be the cause of other anomalies associated with the syndrome.

Heredity

The inheritance pattern of 22q11 deletion syndrome is autosomal dominant, although in most people with the condition (between 85 to 90 per cent) the syndrome is a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent.

Consequently, parents with a child with a new mutation have little chance of having another child with the disorder. If more than one child with 22q11 deletion syndrome is born in the same family, this may indicate germinal mosaicism. This means that one of the parents carries the mutation in some of his/her reproductive cells but not in the others. In such cases the parent is not sick but risks passing on the mutation to his/her children via his/her reproductive cells. The new genetic mutation the child carries will be hereditary and, as an adult, a person with this mutation risks passing on the deletion to his/her children.

An autosomal dominant pattern of inheritance means that one of the parents has the disease, and so has one normal and one deleted chromosome. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. It is not possible to predict the seriousness of the child’s symptoms. Children who do not have the deleted chromosome do not have the disease and do not pass it on.

Figure: Autosomal dominant inheritance

Symptoms

Every individual with the 22q11 deletion syndrome is unique. The number of symptoms and their severity vary, even though most people have the same deletion. A parent with very mild symptoms, who may not even know that he or she has a chromosome deletion, may have a child with far more severe symptoms. The reverse situation can also arise, where the child’s symptoms are less severe than the parent’s.

The syndrome can affect many parts of the body including the immune and nervous systems, and may cause congenital heart defects. It may also give rise to cleft palate and weakness in the roof of the mouth, causing speech problems. When the nervous system is affected, this often causes delayed development, mild to moderate learning difficulties, and neuropsychiatric problems.

Symptoms vary with age. Cardiac defects, feeding difficulties, frequent infections, and speech and language problems dominate for younger children, while learning difficulties and neuropsychiatric problems become apparent later. Certain facial characteristics are common and include a broad nose with a rounded tip, short palpebral fissures (the distance between the inner and outer corners of the eye lids), hooded eyelids, narrow mouth, small chin, flat cheekbones, and rounded ears.

The heart

Slightly more than half the people with the syndrome have congenital heart defects. Defects are often found in the outflow tracts of the heart. There may be many different kinds of cardiac abnormalities, ranging from mild to more severe. Examples of the most common heart defects are interrupted aortic arch, narrowing of the pulmonary artery (pulmonalis stenosis), total blockage of the pulmonary artery (pulmonalis atresia), remaining common stem extending from the heart to the aorta and the pulmonary artery (truncus arteriosus), or a hole in the wall separating the lower chambers of the heart (VSD, ventricle septum defect) and a combination defect including, among other things, constriction of the outflow to the pulmonary artery and a hole in the wall separating the lower chambers of the heart (tetralogy of Fallot). All these heart defects generally present with symptoms early, often during the first few days or weeks of life.

The mouth and teeth

Cleft palate and poor palate function both occur frequently. The most common types of clefting are isolated cleft palate or submucous cleft palate, which is not immediately apparent. Sometimes there may be complete lip, jaw, and palate clefting. Irrespective of whether or not the palate is cleft, most people with the syndrome also have poor palate function (Velo Pharyngeal Insufficiency = VPI). This means that the back of the roof of the mouth (the soft palate) does not properly close off the oral cavity from the nasal cavity to permit speech and swallowing. When the roof of a newborn infant’s mouth is malformed, the infant will often find it difficult to suck, and milk will often come out of the child’s nose. Later in life, VPI leads to slurred pronunciation and often to very open, nasal speech owing to leakage of air up into the nose.

Feeding difficulties are frequent. It is difficult for infants with the condition to suck, and they often vomit their food through the nose. These feeding difficulties are mainly caused by poor palate function, but may also be attributable to cardiac weakness or disturbed motor development in the gastrointestinal tract. Somewhat older children may have difficulties becoming accustomed to solid foods.

The teeth may have poorly mineralised enamel and can erupt late. Sometimes, certain teeth never erupt at all. Mouth dryness and poor saliva secretion are common. Some individuals with the syndrome have problems with severe caries (dental decay) and gum infections.

Immune deficiencies

Immune system problems are usually mild to moderate, although only a few children will have serious immunodeficiencies. The immunodeficiency is caused by underdevelopment of the thymus. The thymus is formed during the foetal period, when it is located at the top of the throat in front of the oesophagus, to migrate later down to the upper chest cavity. White blood cells known as T-lymphocytes mature in the thymus. The primary function of these white cells is to protect the body against viral infections and coordinate functions in the human immune system.

If the thymus is missing, the child will be born with a severe immunodeficiency and will be at risk of developing life-threatening infections. This is, however, rare. It is more common for the thymus to be small at birth, and not to have migrated down to its proper place in the chest cavity. This leads to a minor to moderate immunodeficiency that presents mainly as increased vulnerability to infections. Upper respiratory tract infections and ear infections are the most common.

In the majority of individuals, this increased susceptibility to infections spontaneously rectifies, and is more or less normal during the course of the child’s preschool and school years. However, the immunodeficiency can last into adult life, with an increased vulnerability to infections and fatigue, as well as increased risk of autoimmune diseases in which the immune system of the body attacks its own cells. In certain cases, an immune deficiency with an antibody (immunoglobulin) deficiency can develop.

Calcium deficiency

Low levels of calcium in the blood are caused by underdeveloped or, in rare cases, absent parathyroid glands. The result is low levels of the hormone PTH (parathyroid hormone), which is normally produced by these glands. The parathyroid hormone is important in regulating the calcium metabolism. Symptoms of low calcium levels may present in infancy as bouts of trembling, both longer-lasting and more pronounced than normally seen in newborns. The body needs a great deal of parathyroid hormone in the neonatal period, but less thereafter. Calcium deficiency is often spontaneously corrected although it may remain a latent problem recurring in stressful situations, for example in connection with surgery.

Low blood calcium levels can also give symptoms such as muscle cramps, fainting, or epileptic seizures. Other, more diffuse symptoms may also occur, including muscular weakness, numbness, prickling sensations, anxiety, tiredness and sleeping problems. Aching legs, often interpreted as growing pains, may be attributable to low blood calcium levels. Even if individuals with 22q11 deletion syndrome do not have a calcium deficiency as young children, it may develop in later life.

Growth

Short stature and low weight are common among neonates and children up to the age of about six. Weight often becomes normal but final height is often below average, even if there are large variations in height and weight between people with the syndrome. It is only in a few people with the condition that the production of the growth hormone is impaired, and growth hormone treatment is given only when the deficiency has been confirmed.

Development

In most people with the condition, cognitive development is delayed. Studies show that almost half of those tested have a mild intellectual disability and while cognitive development may be within the normal range, it is nevertheless below average. The intellectual profile of people with the syndrome may be uneven. Intellectual functions controlled by the right hemisphere of the brain, including awareness of shapes and the ability to receive and interpret signals from the eye (visual perception) are often less-well developed than language functions, which are commonly controlled by the left hemisphere.

Speech and language acquisition are delayed. Many children with the syndrome do not begin to speak until the age of two or three, and some even later. Using language may continue to be difficult for older children, many having a tendency to speak in short, simple sentences. Many individuals with the syndrome have limited facial expression, which can make communication more difficult. Sometimes children with the syndrome have difficulty remembering longer, verbal instructions. To ensure that the information is understood, it is important that speakers divide it up, giving a little at a time.

Abnormalities of motor control are common. For some individuals, the main problem is poorly-developed gross motor skills (balance, running, jumping, muscular strength), while for others the primary problem is with fine motor development (finger skills, hand-eye control).

Neuropsychiatric problems are common. These include attention deficits and difficulties with social interaction. Many of these children are diagnosed as suffering from ADHD (attention deficit hyperactivity disorder). Their mental energy level is often low, which may result in concentration and attention difficulties, as well as diminished stamina. A few children with the syndrome who have specific problems with social interaction and communication may have some form of autistic spectrum disorder, but most are diagnosed with an autism-like condition.

The combination of low intellectual level or developmental delay, with limited concentration, stamina and visual perception, results in learning difficulties which become more pronounced as the child becomes older and educational demands increase.

Psychiatric symptoms of different kinds have been described as common in adults with 22q11 deletion syndrome. Anxiety and depressive states are identified most frequently, as well as manic depression (bipolar affective disorder), schizophrenia and schizophrenia-like conditions.

Other points

Eye problems, including impaired vision, severe astigmatism, and squinting are frequent.

Ear problems, including ear infections, fluids in the middle ear, and problems with wax in the auditory canals are also common. Many of these children have slightly impaired hearing, and a small number have more severe hearing deficiencies.

Other malformations and abnormalities may also be seen, but less frequently. These include malformations of the urinary tract, the feet, the skeleton, the brain and the gastrointestinal tract. Scoliosis (curvature of the spine) is also common.

Diagnosis

Symptoms including heart defects, feeding problems, sensitivity to infection, delayed development and unclear, nasal speech can indicate 22q11 deletion syndrome. The deletion in 22q11 can be detected through a genetic test to identify mutations and should always be done when there is reason to suspect that an individual might have the syndrome. An ordinary chromosome analysis on cultured blood cells seldom reveals the deletion, although such tests may be useful for discovering further chromosomal aberrations.

At the time of diagnosis it is important that the family is offered genetic counselling. Carrier and prenatal diagnosis, as well as pre-implantation genetic diagnosis (PGD) in association with IVF (in vitro fertilization), are available in families where the deletion is known.

Treatment/interventions

It is essential that treatment is coordinated by a multidisciplinary team with experience of the syndrome.

A cardiac examination and assessment should be carried out. Children with complex heart defects need to be examined by a paediatric cardiologist and, when necessary, referred for surgery. Such surgery can currently be performed in Gothenburg and Lund. Sometimes operations have to be carried out in different stages, and on separate occasions. Even for children with serious heart defects, the prognosis is good.

Because many of the children with the syndrome have eating difficulties, it is important to consult a dietician and a speech therapist. Some very young children may need to be tube-fed through a nasal-gastric tube for a period of time.

The immune system must always be investigated. This is done through blood test analysis. Children who suffer from frequent infections may need preventive antibiotic treatment for shorter or longer periods of time. Children and adults with pronounced immune deficiencies will require particular measures to avoid infection. They should not, for example, be vaccinated with live vaccines against measles, mumps, rubella and tuberculosis. Treatment with immunoglobulins (antibodies) may sometimes be necessary. If they should require blood transfusions, the blood and plasma products should be radiated. In some very rare cases, the immune deficiency may be so severe as to result in life-threatening infections. It should always be noted that people with 22q11 deletion syndrome have a tendency to acquire repeated infections.

The function of the parathyroid glands should be regularly tested with the help of blood samples, particularly before any surgical procedures. This applies to both adults and children. Thyroid function should also be frequently monitored, as there is an increased risk of hypothyroidism (under active thyroid). Loss of function should receive medical treatment.

When a growth hormone deficiency has been confirmed, growth hormone treatment is given in the form of daily injections. Treatment may even be needed in adulthood if there is a pronounced growth hormone deficiency, because growth hormone not only affects growth but is also an important regulator of the metabolism.

Vision and hearing should also be checked early. Some children will require glasses, and children with more severe hearing impairments will need hearing aids.

Early contact should be established with a paediatric dental specialist for an assessment. If the syndrome is discovered in adulthood, an examination can be made by a hospital dentist or at an oral medicine clinic. Salivary secretion and the presence of caries bacteria in the saliva should be monitored several times as the child is growing up, and every fifth year in adulthood. Most children with the syndrome require additional preventative dental care in the form of fluoride treatment and help with tooth brushing. Between the ages of seven to nine there should be a thorough dental and orthodontic examination. If an individual has a heart abnormality, or is about to undergo heart surgery, preventative treatment with antibiotics should be initiated in order to stop the spread of bacteria in the blood stream. This applies, for example, to dental treatment which may cause bleeding. This is done to prevent bacteria from reaching the heart and causing serious infections.

As speech and language development is often delayed it is important that a speech therapist is contacted at an early stage, to examine the child and assess possible treatments. Palate function should be assessed by both a specially-trained speech therapist and a physician specializing in voice and speech development (a phoniatrician). If the child has a cleft palate, surgery is performed by a specialist plastic surgeon in several stages as the child is growing up. Many children with defective palates may require pharyngeal flap surgery. This surgery, in combination with speech therapy, can improve palate function and thus speech.

Habilitation

Most children require habilitation from an early age. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment are offered within the medical, educational, psychological, social and technical fields. Measures may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling. It also includes information on support offered by the local authority, and advice on adapting accommodation and other environments. The family may also need help in coordinating different forms of help. Adults with the syndrome may require continued habilitation measures.

Habilitation is planned on the basis of existing needs in order to create prerequisites for the best possible future outcome. Habilitation may vary over time, and always takes place in collaboration with individuals close to the child. It is important that the psychological and social needs of the whole family are met.

When the child’s language and speech development is delayed, an investigation is carried out which will form the basis for the chosen method of communication. Some children need to use augmentative and alternative communication (AAC) for a period in order to be able to communicate with those around them in the best way possible.

A physiotherapist and occupational therapist can evaluate the development of fine and gross motor skills and provide advice on suitable exercises. The intellectual development of the child should be assessed by a psychologist. Usually the assessment needs to be repeated on several occasions. For most children with the syndrome, a more extensive neuropsychiatric assessment will be needed. This will include a neuropsychological assessment.

Information and planning in good time before the child starts school are important for the child’s school career. The combination of intellectual disability or developmental delay, lack of concentration, stamina and visual perception means that most children with the syndrome will require a great deal of help in school, in the form of special education. Educational methods will have to be adapted to the abilities and intellectual level of each child. Good support from a peer group is also important.

Some adults with the syndrome may require continued habilitation and many need contact with adult psychiatric services.

Practical advice

--

National and regional resources in Sweden

Specialist team for diagnostics, examination and treatment:

In Sweden there are two specialist teams, one in Gothenburg and one in Stockholm. The teams include a paediatrician, an audiologist, an endocrinologist, a phoniatrician, a geneticist, an immunologist, a cardiologist, a speech therapist, a neuropsychiatrist, a plastic surgeon, a psychologist, an ophthalmologist, an ENT specialist and a dentist.

Contact person for the Gothenburg team is Senior Physician Sólveig Óskarsdóttir, Paediatric Immunology, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

The contact person for the team is Senior Physician Britt-Marie Anderlid, Astrid Lindgren Children’s Hospital and Department of Clinical Genetics, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Genetic diagnostic tests are performed in Departments of Clinical Genetics at Swedish university hospitals.

Expertise in orofacial problems can be found at Mun-H-Center, Institute of Odontology in Gothenburg, Medicinaregatan 12A, SE-413 90 Gothenburg, Sweden. Tel: +46 31 750 92 00, fax: +46 31 750 92 01, email mun-h-center@vgregion.se, www.mun-h-center.se.

Resource personnel

Senior Physician Sólveig Óskarsdóttir, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00, fax: +46 31 707 06 94, email: solveig.oskarsdottir@vgregion.se.

Senior Physician Vanda Friman, Infection Clinic, Sahlgrenska University Hospital/Östra, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Senior Physician Britt-Marie Anderlid, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Professor Elisabeth Syk Lundberg, Clinical Genetics, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 753 80, fax: +46 8 32 77 34.

Professor Christopher Gillberg, Lena Niklasson (neuropsychologist), Associate Professor Peder Rasmussen, Section for Neurology, Neuropsychiatry and Habilitation, The Queen Silvia Children’s Hospital, Box 171 13, SE-402 61 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Christina Persson, (speech and language pathologist), Speech Therapy and Phoniatrics Clinic, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Tel +46 31 342 10 00.

Courses, exchanges of experience, recreation

Ågrenska is a national competence centre for rare diseases and its families’ programme arranges stays for children and young people with disabilities and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare diseases. A number of programmes are also provided for adults with rare diseases. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

Organizations for the disabled/patient associations etc.

Föreningen 22q11, (the Swedish 22q11 Association), c/o RoseMarie Larsson, Norgårdsvägen 17, SE-430 90 Öckerö, Sweden. Email: r-marie@telia.com, www.22q11.se.

Rare Diseases Sweden, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Diseases Sweden is a national association promoting the interests of people with rare diseases and various disabilities.

The Swedish Children’s Heart Association, Kammakaregatan 47, SE-111 24 Stockholm, Sweden. Tel: +46 8 442 46 50, email: kansliet@hjartebarn.org, www.hjartebarn.org.

Courses, exchanges of experience for personnel

During the Ågrenska Family Program weeks, training days are organized for personnel working with the children and the young people who are participating. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

Research and development

In Sweden, research is being carried out at the Queen Silvia Children’s Hospital in Gothenburg, The Division of Speech and Language Pathology at Sahlgrenska Academy at Gothenburg University, and at the Mun-H-Center. (See under “National and regional resources”). Extensive research is also being carried out internationally.

Information material

Short summaries of all the database texts are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version, and then clicking on the leaflet icon which will appear under, “Mer hos oss” in the column on the right-hand side.

Newsletters from Ågrenska on 22q11 deletion syndrome, no. 200 (2002), and no. 353, (2009). (In Swedish only.) Newsletters are edited summaries of lectures delivered at family and adult visits to Ågrenska. They may be ordered from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se.
They are also available at www.agrenska.se.

DiGeorges syndrom (22q11.2 delesjonssyndrom). In Swedish only. Leaflet no. 41 (In Norwegian only) from Frambu, Senter for sjeldne funksjonshemningar (2006). Order from: Frambu, Senter for sjeldne funksjonshemninger, Sandbakkveien 18, NO-1404 Siggerud, Norway. Tel: +47 64 85 60 00, info@frambu.no, www.frambu.no.

Literature

Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A et al and The International 22q11.2 Deletion Consortium. Practical guidelines for managing patients with 22q11.2 deletion syndrome. Pediatr 2011; 159: 332-339.

Bassett AS, Chow EW, Husted J, Weksberg R, Caluseriu O, Webb GD, Gatzoulis MA. Clinical features of 78 adults with 22q11 Deletion Syndrome. Am J Med Genet A 2005; 138: 307-313.

Björk AH, Óskarsdóttir S, Andersson BA, Friman V. Antibody deficiency in adults with 22q11.2 deletion syndrome. Am J MedGenet A 2012; 158: 1934-1940.

Butcher NJ, Chow EW, Costain G, Karas D, Ho A, Bassett AS. Functional outcomes of adults with 22q11.2 deletion syndrome. Genet Med 2012; 14: 836-843.

Casteels I, Casaer P, Gewillig M, Swillen A, Devriendt K. Ocular findings in children with a microdeletion in chromosome 22q11.2. Eur J Pediatr 2008; 167: 751-755.

Gennery AR. Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci 2013; 69: 17-27.

Habel A, McGinn M-J, Zackai EH, Unanue N, McDonald-McGinnDM. Syndrome-specific growth charts for 22q11.2 deletion syndrome in caucasian children. Am J Med Genet Part A; 158: 2665-2671.

Kapadia CR, Kim YE, McDonald-McGinn DM, Zackai EH, Katz LE. Parathyroid hormone reserve in 22q11.2 Deletion Syndrome. Genetics in Medicine 2008; 10: 224-228.

Karas DJ, Costain G, Chow EW, Bassett AS. Perceived burden and neuropsychiatric morbidities in adults with 22q11.2 deletion syndrome. J Intellect Disabil Res. 2012 Oct 29. doi: 10.1111/j.1365-2788.2012.01639.x. [Epub ahead of print]

Klaassen P, Duijff S, Swanenburg deVeye H, Vorstman J, Beemer F, Sinnoma G. Behavior in preschool children with the 22q11.2 deletion syndrome. Am J Med Genet A 2013; 161: 94-101.

Klingberg G, Oskarsdóttír S, Lingström P, Carlén A, Norén JG, Friman V. Ett ovanligt vanligt syndrom. Tandläkartidningen 1999; 7 2007: 54-59.

Lima K, Abrahamsen TG, Wolff AB, Husebye E, Alimohammadi M, Kömpe O, Fölling I. Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome. Eur J Endocrinol 2011; 165: 345-352.

Michaelovsky E, Frisch A, Carmel M, Patya M, Zarchi O, Green T et al. Genotype-phenotype correlation in 22q11.2 deletion syndrome. BMC Med Genet 2013; 13: 122.

Niklasson L, Rasmussen P, Oskarsdottir S, Gillberg C. Autism, ADHD, mental retardation and behavior problems in 100 individuals with 22q11 deletion syndrome. Res Dev Disabil 2009; 30: 763-773.

Niklasson L, Gillberg C. The neuropsychology of 22q11 deletion syndrome. A neuropsychiatric study of 100 individuals. Res Dev Disabil 2010; 31: 185-194.

Oskarsdóttir S, Holmberg E, Fasth A, Strömland K. Facial features in children with the 22q11 deletion syndrome. Acta Paediatr 2008; 97: 1113-1117.

Óskarsdóttir S, Vujic M, Fasth A. Incidence and prevalence of the 22q11 deletion syndrome: a population-based study in western Sweden. Arch Dis Child 2004; 89: 148-151.

Óskarsdóttir S, Persson C, Eriksson BO, Fasth A. Presenting phenotype in 100 children with 22q11 deletion syndrome. Eur J Pediar 2005; 164: 146-153.

Óskarsdóttir S, Belfrage M, Sandstedt E, Viggedal G, Uvebrant P. Disabilities and cognition in children and adolescents with 22q11 deletion syndrome. Dev Med Child Neurol 2005; 47: 177-184.

Óskarsdóttir S, Fasth A, Belfrage M, Viggedal G, Persson C, Eriksson BO. CATCH 22-syndrom/22q11deletion ssyndrom: Underdiagnosticerad missförstådd sjukdomsgrupp med skiftande klinisk bild. Läkartidningen 1999; 96: 4789-4793.

Óskarsdóttir S, Fasth A, Niklasson L, Rasmussen P, Gillberg C. 22q11deletion (CATCH 22) - förbisedd orsak till medicinska problem i kombination med neuropsykiatriska funktionshinder. Socialmedicinsk tidskrift 2001; 78: häfte 2.

Persson C, Friman V, Óskarsdóttir S, Jönsson R. Speech and hearing in adults with 22q11.2 deletion syndrome. Am J Med Genet A 2012; 158: 3071-3079.

Persson C, Lohmander A, Jonsson R, Óskarsdóttir S, Söderpalm E. A prospective cross-sectional study of speech in patients with the 22q11 deletion syndrome. J Commun Disord 2003; 36: 13-47.

Persson C, Niklasson L, Óskarsdóttir S, Johansson S, Jonsson R, Söderpalm E. Language skills in 5-8-year-old children with 22q11 deletion syndrome. Int J Lang Commun Disord 2006; 41: 313-333.

Saitta SC, Harris SE, Gaeth AP, Driscoll DA, McDonald-McGinn DM, Maisenbacher MK et al. Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion. Hum Mol Genet 2004; 13: 417-428.

Sullivan KE. The clinical, immunological and molecular spectrum of chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Curr Opin Allergy Clin Immunol 2004; 4: 505-512.

Swillen A, Vogels A, Devriendt K, Fryns JP. Chromosome 22q11 deletion syndrome: update and review of the clinical features, cognitive-behavioural spectrum, and psychiatric complications. Am J Med Genet 2000; 97: 128-135.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: digeorge syndrome, velocardiofacial syndrome

GeneReviews (University of Washington)
www.genetests.org (select “GeneReviews”, then “Titles”)
Search: 22q11.2 deletion syndrome

Orphanet, European database
www.orpha.net 
Search: monosomy 22q11

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Senior Physician Sólveig Óskarsdóttir, The Queen Silvia Children’s Hospital, Gothenburg, Sweden.

The relevant organizations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2014-03-24
Version: 3.0
Publication date of the Swedish version: 2013-10-30

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.