22q11.2 deletion syndrome is highly variable and may present with any combination of the features listed below.
|Commonly associated features|
|Congenital heart disease||Often conotruncal, ventricular septal defect, Tetralogy of Fallot, Interrupted aortic arch, truncus arteriosus|
|Palatal anomalies||Velopharyngeal insufficiency, hypernasal speech, cleft palate (typically submucosal), bifid uvula, dysphagia|
|Laryngotracheoesophageal anomalies||Laryngomalacia, vascular ring, subglottic stenosis|
|Developmental delay and/or learning difficulties||Variable, even within families; more significant speech delay|
|Neuropsychiatric||Autism spectrum disorder, attention deficit disorder, schizophrenia, anxiety|
|CNS||Hypotonia, microcephaly, seizures (may be associated with hypocalcaemia)|
|Gastrointestinal||Hernias, constipation (with or without a structural cause)|
|Immunological||Frequent infections/immune deficiency (thymic hypoplasia and subsequent impaired T-cell production), predisposition to autoimmune conditions|
|Ophthalmologic and audiological||Ptosis, strabismus, coloboma, cataract, hearing loss (sensorineural and/or conductive)|
|Facial features (variable and not always present)||Hooded eyelids, flat nasal bridge, bulbous nasal tip, micrognathia, asymmetric crying facies, craniosynostosis, small, low-set ears, overfolding, cupped shape, preauricular tags and pits|
|Skeletal||Occipital-cervical anomaly, rib and vertebral anomalies, scoliosis, clubfoot, extra fingers|
|Genitourinary||Renal anomalies, cryptorchidism, hypospadias|
|Endocrine||Hypoparathyroidism and hypocalcaemia, hypothyroidism, growth hormone deficiency|
22q11.2 deletion syndrome is caused by a microdeletion at chromosome position 22q11.2. The microdeletion is typically 2.54 Mb in size. Individuals with 22q11.2 deletion syndrome have one, rather than the usual two, copies of a number of genes, including the gene TBX1.
Note that significantly smaller or larger deletions in, and distal to, this region do occur and can cause different medical problems.
Inheritance and genetic counselling
Most cases of 22q11.2 deletion syndrome arise because of a new (de novo) microdeletion occurring in the egg or sperm.
The features of this condition can be extremely variable, however, even within members of the same family. As such, it is important to offer testing to parents, even if they do not have any apparent symptoms. If a parent is found to have a 22q11.2 deletion, they should be offered the opportunity to access genetic counselling and health screening.
When an individual with 22q11.2 deletion syndrome has children, there is a 50% chance of passing on the microdeletion in each pregnancy. If a parent is found to have a 22q11.2 deletion, existing and future siblings may be affected. Individuals with 22q11.2 deletion syndrome may wish to discuss reproductive options, which could include testing in pregnancy (prenatal diagnosis) or preimplantation genetic diagnosis.
Management of children with 22q11.2 deletion syndrome is complex and should be delivered via a multidisciplinary team, with detailed suggested approaches published by several authors. See the resources for clinicians, below.
- Gene Reviews: 22q11.2 deletion syndrome
- NHS England: National Genomic Test Directory and eligibility criteria
- US National Institutes of Health: 22q11.2 deletion syndrome
- Habel A, Herriot R, Kumararatne D and others. ‘Towards a safety net for management of 22q11.2 deletion syndrome: guidelines for our times.’ European Journal of Paediatrics 2014: volume 173, issue 6, pages 757-65. doi: 10.1007/s00431-013-2240-z