Despite 22q11 deletion syndrome (22q11DS) being the most common recurrent copy-number variant disorder, it is one few medical students have a clear understanding of. It is caused by a microdeletion occurring in chromosome band 22q11.2 and a 2004 study estimated it to have an incidence of approximately 1 in 4000 individuals.¹

Some of the confusion may stem from the fact that the syndrome may also be known as Shprintzen’s syndrome or velocardiofacial syndrome (VCFS), while research has confirmed that Cayler’s syndrome, Di-George Syndrome, and Takao’s syndrome are all caused by the same deletion.²  The various names dictate the severity of the disorder, with VCFS representing the mild to moderate range while Di-George is the more severe end of the scale.  Although the condition may not be one medical students encounter on a regular basis, it can present with a variety of complications and associated conditions, meaning it is worthwhile for medical students to fully understand the condition as well as the impact it has on both the patient and their family.

22q11DS may present in a wide range of out-patient clinics from cardiology to psychiatry. The condition can present with a variety of clinical syndromes including cardiac abnormalities, palatal anomalies, thymus aplasia, hypocalcaemia, speech and language delays, reduced immunity, parathyroid hypoplasia, and dental problems. Approximately 75% of those affected by a 22q11DS have some form of cardiac issue, with the most common of these being tetralogy of Fallot, interrupted aortic arch, and ventricular septal defect. A number of medical textbooks discuss the ‘typical facial features’, however, the physical appearance of a person with 22q11DS can vary hugely. Up to 60% of those affected have some degree of velopharyngeal insufficiency. Other palatal anomalies include cleft palate or submucous cleft. Cleft lip can occur in a smaller number of children.

In addition, 35% of individuals with 22q11DS will have some degree of renal problems, most commonly renal agenesis. Musculoskeletal problems include scoliosis , vertebral abnormalities, Sprengel’s shoulder, talipes, and rheumatoid arthritis. Children affected by any of the above will require surgical review, liaison with physiotherapy, and appropriate pain management.

It is estimated that about 50% of those with a 22q11DS have a normal level of intelligence, but up to 65% of children with 22q11DS may have some form of learning difficulty. Although a large number of 22q11DS patients having an intellectual disability, they are rarely severe. The most common difficulty is usually related to abstract reasoning or planning ability.  Several studies have examined the wide range of psychiatric disorders that patients with a 22q11DS may also present with, including attention deficit disorder, autism, anxiety, obsessive compulsive disorder, and depression³. Up to 30% of patients may also develop schizophrenia and schizoaffective disorder, most commonly presenting late in adolescence³.

22q11DS is diagnosed via a positive FISH test. Parents of an affected child might opt to be tested but it is worth noting that only 10-15% of parents will be carriers of the deletion. An affected parent has a 50% chance of passing on the condition to their offspring. The parents of an affected child have only a 1-2% chance of having a child with a 22q1DS in any subsequent pregnancies. The condition can be diagnosed in utero at 11 weeks through chorionic villus sampling or by amniocentesis from week 16 onwards. Standard fetal ultrasounds allow the opportunity for early identification of cardiac anomalies. In Ireland, ‘22q11 Ireland’ provides excellent support for people with a 22q11DS and their families.⁴ The parent-led voluntary group is working towards more integrated care for people with a 22q11DS.

As previously mentioned, 22q11DS is not something medical students would generally feel confident discussing. However, the wide spectrum of health issues these patients can present with means that medical students should indeed be aware of the syndrome, its variants, and its impact on patient health and quality of life.

References

1. Oskarsdottir S, Vujic M and Fasth A (2004) Incidence and prevalence of the 22q11 deletion syndrome: a population based study in Western Sweden. Archives of Disease in Childhood 89, 148-51
2. McDonald McGinn DM and Sullivan KE (2011) Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine 90, 1-18
3. Evers LJM et al (2014) Psychopathology in adults with 22q11 deletion syndrome and moderate and severe intellectual disability. Journal of Intellectual Disability Research 58 (10) 915-25
4. 22q11ireland.org