22q Frequently Asked Questions (2024)

22q11.2 deletion syndrome is a chromosomal abnormality that can cause a wide range of health and developmental issues, including heart defects, breathing issues, problems with the gastrointestinal tract, immune and endocrine systems, differences in the palate, slow growth, autism/developmental delays or learning disabilities in some individuals.

Children with this condition may have many or only a few of the symptoms, with varying severity. Physicians with expertise in this condition can quickly recognize the diagnosis in some patients and take steps to improve their quality of life, but in other children and adults it is not as straightforward.

Most times the deletion is not hereditary or “running in the family” but once it is present the person with the deletion has a 50% chance of passing it on to his or her child. It is important to know that the eggs and sperm have no memory so every pregnancy has the same 50% chance of having a child with the deletion even if there is an affected child already in the family. In addition, as the findings in people with the 22q11.2 deletion are variable it is impossible to predict how mildly or significantly affected a child will be.

When neither parent has the deletion it is said that it “just happened” in their child – that is a chance occurrence. It is nothing that the parents did or did not do that caused it to occur. It occurs on a very cellular level due to the inherent structure of the chromosome and it is nothing that anyone has any control over. This is very important as many families feel a sense of guilt over the fact that their child has a “genetic condition” but this is not anyone’s fault.

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

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

Unlike the early reports on children with DiGeorge syndrome, many of whom died in early infancy prior to the availability of sophisticated cardiac surgeries and antibiotics to fight infections, the mortality rate in children with the 22q11.2 deletion is very low (~ 4%) and those children who do succumb to problems associated with the deletion often pass away at a very young age (~ 4 months). However, many children and adults have numerous medical problems across their lifetime that requires specialized care. These include:

• Cardiology– where 75% of children have some type of heart defect, many of whom require surgery to correct the problem, often in the newborn period.
• Child Development– where most children (>95%) have motor milestone delays (like walking), delays in emergence of language and specific learning differences requiring special help in school; and a subset of children have autism or autistic like features and/or behavioral differences like ADHD, OCD, anxiety, perseverations, and psychosis. It is important to note that all children benefit from Early Interventions strategies including such things as occupational therapy, physical therapy, and speech therapy/sign language in young childhood followed by specific learning style interventions as most children have relative strengths in reading and rote memorization but more difficulty with math and complex/abstract reasoning (a non-verbal learning disability).
• Cleft Palate Team– where 75% of children have differences in their palate allowing milk to come through their nose in infancy (known as nasal regurgitation) and later causing them to have hypernasal speech which makes it difficult for the child to be understood. Here too, many children benefit from surgical interventions, usually performed by a Plastic Surgeon or an ENT as part of a Cleft Palate Team.
• Endocrinology– where 50% of children have low calcium levels which usually resolve in infancy, but some children require calcium supplements for a longer period of time or during times of illness or stress such as at puberty or post operatively; in addition, some children have trouble with their thyroid (under active or over active) and some have growth hormone deficiency –all of which respond to treatment.
• ENT and Audiology– where ear infections are common (often due to the high incidence of palatal problems), as is the presence of hearing loss (both conductive and sensorineural), and problems with the child’s airway due to structural differences such as a vascular ring or laryngeal web or associated with reflux. Occasionally a child will have a connection between the wind pipe and feeding pipe (tracheoesophageal fistula) or an abnormal feeding pipe (esophageal atresia). Many children benefit from ear tube placement; some need hearing aides; whereas others require more complex care from an Otolaryngologist.
• Gastroenterology/Feeding Team– where 35% of children have significant feeding and swallowing problems such as gastroesophageal reflux (GERD) and dysmotility leading to reflux and constipation; less common problems include umbilical hernia, intestinal malrotation, an absent anal opening, Hirshsprung’s disease (where the child has severe constipation/blockage of the bowel), a diaphragmatic hernia where loops of bowel can be in the chest. Most common feeding problems exist in the newborn period and often resolve with medical assistance by school age.
• Hematology/Oncology– where rarely a child has had problems with bleeding due to the deletion of a gene that codes for clotting on the chromosome with the deletion and a non-working gene on the other chromosome 22 called Bernard-Soullier syndrome and occasionally children have had problems with their blood counts due to an autoimmune problem such Idiopathic Thrombocytopenia and Autoimmune Neutropenia; some children have rarely had a tumor, most notably in the liver (hepatoblastoma) and sometimes elsewhere such as the kidney (Wilm’s tumor, Renal Cell carcinoma) or thyroid; as well as an occasional individual with Leukemia or Lymphoma. With the exception of Bernard-Soullier syndrome, these problems are likely related to the individuals’ “pokey” immune system as well as other genes on other chromosomes that may predispose them to having these problems.
• Immunology/Rheumatology– where 77% of children have immunodeficiency regardless of whether or not they appear to have recurrent infections including things like recurrent infections, not mounting a normal response to vaccines, and not being able to receive live viral vaccines. Most problems resolve in infancy but some older children and adults have chronic infections. In addition, children and adults are more prone to autoimmune diseases such as Juvenile Rheumatoid arthritis, Idiopathic Thrombocytopenia, Autoimmune Neutropenia, Grave’s disease, and Vitiligo.
• Neurology– where, rarely, children have seizures unrelated to their low calcium levels and/or structural brain differences/a small head. An occasional child will have spina bifida.
• Ophthalmology– where some children have eye problems such as droopy eyelids (known as ptosis); differences in the whites of their eyes (scleracornea); differences in the colored parts of their eyes (coloboma); and differences with their eye muscles. Some of these problems need surgical treatment or other interventions such as patching of the eyes and others do not.
• Orthopaedics– where 50% of children have differences in the way the vertebrae of the spine are formed at the neck causing decreased room surrounding the spinal cord at the neck in a very small subset of children which often benefit from surgical correction; differences in the bones of the spine in other areas such as the chest (butterfly vertebrae); curvature of the spine (scoliosis); extra ribs, extra fingers and toes; differences in “wing bones (scapula); and occasionally premature fusion of the bones of the skull (craniosynostosis) all of which are able to be helped surgically if needed. Many children also have unexplained leg pain.
• Urology– where 35% of children have differences in the way their kidneys are formed or how they work such as a single or malformed kidney and/or kidney reflux, as well as, problems with infections, potty training, and differences in the way the genito-urinary system may be formed (hypospadias in boys where the opening of the penis is not at the tip and undescended testes and occasionally an absent uterus in girls); and hernias in the groin.

Ideally, children with the 22q11.2 deletion receive coordinated care in centers comprised of multidisciplinary teams of clinicians often drawn from more than 20 specialties. Centers address each child’s individual health problems, as well as issues such as speech or learning delays in order to help these children and their families lead the best life possible. Upon initial diagnosis the standard assessment and work up for all ages generally includes:

• Cardiology
• Endocrinology
• Immunology
• Speech/Language/Developmental Assessments

As well as:

• A Renal Ultrasound (to check the kidneys)
• X-rays of the neck (in children old enough to cooperate and where the bones are well ossified – so 3 to 4 years of age)
• Deletion studies in both parents when available

Thereafter, the work-up is individualized depending on the symptoms but may include any or all of the following:

• Plastic Surgery/ENT/Audiology
• Gastroenterology/Feeding Team
• Hematology
• Urology/Nephrology
• Orthopaedics
• Ophthalmology
• General Surgery
• Dentistry
• Rheumatology
• Neurology/Neurosurgery
• Psychiatry