All About 22q11.2 Deletion Syndrome

22q11.2 Deletion Syndrome (22q) is a disorder caused by a small missing piece of the 22nd chromosome. This tiny missing portion of chromosome 22 can affect every system in the human body. In fact, 22q can be the cause of up to 200 mild to serious health and developmental issues in children and young adults.

You may have come across it being referred to as Velocardiofacial syndrome (VCFS), and/or DiGeorge Syndrome. It is often thought that Down Syndrome is the most commonly recognised chromosome disorder, but it is 22q that is thought to be the second most common. 

What is 22q11.2 Deletion Syndrome?
Due to the chromosomal abnormality of the missing 22nd chromosome, the syndrome can cause a wide range of health and developmental issues, ranging from heart defects, breathing impairments, problems with the gastrointestinal tract, immune and endocrine systems, palate differences, slow growth, autism and/or developmental delays or learning disabilities in some people. 

Children born with this syndrome may have many, or just a few of the symptoms, and the severity can vary from person to person. In fact, every child born with 22q presents a unique set of the possible cc. 200 symptoms, and thus is uniquely difficult for even the best doctors to recognise. 

It is such a unique syndrome, that every child can manifest 22q in multiple ways that are unique to them and them only. 

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You might also be interested in:

• 22q11.2 support groups and charities internationally
• Help raise awareness of 22q in November
• Chat with other mums and women about 22q

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How common is 22q11.2 Deletion Syndrome?
It is believed that the 22q deletion occurs in 1 of 4,000 live births, although this is likely a gross underestimate of this deletion. Plus it is the most frequent cause of syndromic palatal defects (such as a cleft lip and palate), and it is found in 1 of 68 children born with a heart defect. 

Nonetheless, despite this prevalence, many physicians are still not familiar with the diagnosis. 

What tests are used to identify the deletion?
Nowadays, we are medically fortunate to have access to a number of tests that can help to identify the deletion - tests that were not as accessible just a couple of decades ago. The most readily performed method of identification is blood tests. These include: FISH (fluorescence in situ hybridization), comparative genomic hybridization (CGH), whole genome or SNP array, and multiplex ligation-probe amplification (MLPA). 

Is 22q11.2 Deletion Syndrome hereditary?
Most of the time, the deletion does not "run in the family", but once it is present in a person, they have a 50% chance of passing it on to their child. 

When neither parent has the deletion, it is said to have "just happened" in their child, and is a complete chance occurrence. It is nothing the parents have done or did not do that may have caused it to occur. 22q occurs on a very cellular level due to the inherent structure of the chromosome and it's nothing that anyone has any control over. 

Understandably, families may feel a sense of guilt over the fact their child has a "genetic condition", but it is nobody's fault for the above reasons.

What are the symptoms of 22q11.2 Deletion Syndrome?

Most affected symptoms:

• Cardio-vascular
• Cleft palate
• Feeding difficulties
• Immunization problems
• Growth hormone deficiencies
• Delayed neurological and psychological developments
• Speech problems
• Renal abnormalities

Anomaly fact sheet of symptoms:

Abdominal/kidney/gut

• Hypoplastic/aplastic kidney
• Cystic kidneys
• Anal anomalies (displaced, imperforate)
• Inguinal hernias
• Umbilical hernias
• Single case of malrotation of the bowel
• Hepatoblastoma and diaphragmatic hernia (rare)
• Diastasis recti abdominis

Cardiac findings

• VSD (ventricular septal defect)
• ASD (atrial septal defect)
• Pulmonary atresia or stenosis
• Tetralogy of Fallot
• Right-sided aorta
• Truncus arteriosus
• PDA (patent ductus arteriosus)
• Interrupted aorta
• Coarctation of the aorta
• Aortic valve anomalies
• Aberrant subclavian arteries
• Vascular ring
• Anomalous origin of carotid artery
• Transposition of the great vessels
• Tricuspid atresia

Cognitive/learning

• Learning disabilities (math concept, reading comprehension)
• Concrete thinking, difficulty with abstract thinking
• Drop in IQ scores in school years (test artifact)
• Borderline normal intellect (based on 100% as “normal”)
• Occasional mild mental retardation
• Attention deficit hyperactivity disorder (ADD/ADHD)

Craniofacial/oral findings

• Overt, submucous or occult submucous cleft palate
• Retrognathia (retruded lower jaw)
• Platybasia (flat skull base)
• Asymmetric crying facies in infancy
• Structurally and/or functionally asymmetric face
• Straight facial profile
• Cleft lip (uncommon)
• Enamel hypoplasia on teeth (primary dentition)
• Small teeth
• Congenitally missing teeth
• Hypotonic, flaccid facies
• Downturned oral commissures
• Microcephaly (small head)
• Small posterior cranial fossa
• Vertical maxillary excess (long face)
• Tortuous retinal vessel
• Suborbital congestion “allergic shiners”
• Strabismus
• Narrow palpebral fissures
• Posterior embryotoxin
• Prominent corneal nerves
• Cataract
• Iris nodules
• Iris coloboma (uncommon)
• Retinal coloboma (uncommon)
• Small eyes
• Mild orbital hypertelorism
• Mild orbital dystopia
• Puffy eyelids

Ear/hearing findings

• Over-folded helix
• Attached lobules
• Protuberant, cup-shaped ears
• Small ears
• Mild asymmetric ears
• Frequent otitis media
• Mild conductive hearing loss
• Sensorineural hearing loss
• Ear tags or pits (uncommon)
• Narrow external ear canals

Endocrine

• Hypocalcaemia
• Hypoparathyroidism
• Pseudo-hypoparathyroidism
• Hypothyroidism
• Mild growth deficiency, relative small stature
• Absent, hypoplastic thymus
• Poor body temperature regulation

Genito-urinary

• Hypospadias
• G-U reflux
• Cryptorchidism

Immunologic

• Reduced T cell populations
• Frequent lower airway disease (pneumonia, bronchitis)
• Frequent upper respiratory infections
• Reduced thymic hormone

Limb findings

• Small hands and feet
• Tapered digits
• Short nails
• Contractures
• Triphalangeal thumbs
• Soft tissue syndactyly
• Rough, red, scaly skin on hands
• Morphea
• Polydactyly (both preaxial and postaxial)

Nasal findings

• Prominent nasal bridge
• Bulbous nasal tip
• Mildly separated nasal domes
• Pinched alar base, narrow nostrils
• Narrow nasal passages

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Neurological/brain findings

• Periventricular cysts (mostly anterior horns)
• Small cerebellar vermis
• Cerebellar hypoplasia/dysgenesis
• White matter UBO’s (unidentified bright objects)
• Cerebellar ataxia
• Seizures
• Strokes
• Spina bifida/meningomyelocele
• Mild developmental delay
• Generalized hypotonia
• Pharyngeal/laryngeal airway
• Upper airway obstruction in infancy
• Absent or small adenoids
• Laryngeal web (anterior)
• Large pharyngeal airway
• Laryngomalacia
• Arytenoid hypoplasia
• Pharyngeal hypotonia
• Asymmetrical pharyngeal movement
• Thin pharyngeal muscle
• Unilateral vocal cord paresis
• Reactive airway disease
• Spontaneous oxygen desaturation without apnea

Problems in infancy

• Difficulty in feeding, failure to thrive
• Nasal vomiting
• Gastro-esophageal reflux
• Nasal regurgitation
• Irritability
• Chronic constipation (not Hirshprung megacolon)

Psychiatric/psychological

• Bipolar affective disorder]
• Manic depressive illness and psychosis
• Rapid or ultra-rapid cycling of mood disorder
• Mood disorder
• Depression
• Hypomania
• Generalized anxiety disorder
• Schizoaffective disorder
• Impulsiveness
• Flat affect
• Dysthymia
• Cyclomania
• Social immaturity
• Obsessive compulsive disorder
• Phobias
• Exaggerated startle response

Skeletal/muscle/orthopedic/spine

• Scoliosis
• Hemivertebrae
• Spina bifida oculta
• Butterfly vertebrae
• Fused vertebrae (mostly cervical)
• Tethered spinal cord
• Syrinx
• Sprengel’s anomaly/scapular deformation
• Small skeletal muscles
• Joint dislocations
• Chronic leg pains
• Flat foot arches
• Hyperextensible/lax joints
• Extra ribs
• Rib fusion
• Talipes equinovarus (club feet)
• Osteopaenia
• Juvenile rheumatoid arthritis (JRA)

Skin/integument

• Abundant scalp hair
• Thin appearing skin (venous patterns easily visible)
• Roscea

Speech/language

• Severe hypernasality
• Severe articulation impairment
• Language impairment (usually mild delay)
• Dyspraxia
• Velopharyngeal insufficiency (VPI) (usually severe)
• High-pitched voice
• Hoarseness

Vascular anomalies

• Medially displaced internal carotid artery
• Tortuous, kinked, absent or accessory internal carotids
• Jugular vein anomalies
• Small veins
• Circle of Willis anomalies
• Absence of vertebral artery (unilateral)
• Low bifurcation of common carotid
• Tortuous or kinked vertebral arteries
• Raynaud’s phenomenon
• Thrombocytopenia, Bernard-Soulier disease

What are the medical needs if diagnosed with 22q11.2 Deletion Syndrome?
The mortality rate in children with the 22q11.2 deletion is very low (cc.4%) and those children who do succumb to problems associated with the deletion often pass away at a very young age. Nonetheless, many children and adults can have numerous medical problems across their lifetime that requires specialised care.

These include cardiology, child development, cleft palate team, endocrinology, ENT and audiology, gastroenterology/feeding team, immunology/rheumatology, neurology, ophthalmology, orthopaedics and urology.

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SEE ALSO: What is the difference between a learning difficulty and disability?

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What about 22q11.2 Duplication Syndrome?

As well as 22q11.2 Deletion Syndrome, which is the result of the missing 22nd chromosome, the 22q11.2 Duplication Syndrome is also a condition... One which is caused by an extra copy of a small piece of chromosome 22. 

The prevalence of the 22q11.2 duplication in the general population is difficult to determine, as many individuals with this syndrome have no associated syndromes, and their duplication may go undetected throughout their lifetime. 

The duplication syndrome is about as half as common as the 22q11.2 Deletion Syndrome. 

22q11.2 Duplication Syndrome has the potential to affect many systems in the body and may cause a wide range of health problems, and no people are ever exactly alike, even when they have the same syndrome. 

Many people with the duplication have no apparent physical or intellectual disabilities, and those can understandbly go undiagnosed in people. 

The key characteristics of the syndrome include combinations or different degrees of: 

• Heart defects
• Palate differences
• Feeding and gastrointestinal difficulties including reflux
• Immune system defects, including neutropenia
• Growth delays and short stature
• Weak muscle tone or hypotonia
• Hearing loss
• Occasional endocrine issues including low calcium and thyroid differences
• Cognitive, developmental and speech delays
• Frequent upper respitory infections, asthma
• Behavioral and learning differences including ADHD, autism, Asperger Syndrome, etc.
• Seizure disorders
• Macrocephaly or large head