La microdélétion 22q11.2 est le syndrome microdélétionnel le plus fréquent de la population générale. Le phénotype associe des anomalies de l’appareil pharyngé embryonnaire à un phénotype neurocomportemental. La présentation clinique du syndrome est extrêmement variable d’un individu à l’autre, quelle que soit la taille de la délétion, et plus de 180 manifestations ont été décrites, aucune n’étant pathognomonique. Les symptômes psychiatriques, particulièrement de nature psychotique, sont fréquents dans la microdélétion 22q11.2 et de nombreux psychiatres sont amenés à rencontrer ces patients. La prise en charge doit tenir compte des particularités du syndrome. L’évaluation de la neurocognition, de la cognition sociale et la recherche de symptômes psychiatriques dans le contexte médical général sont une étape fondamentale. Concernant le phénotype neurocomportemental, les soins de remédiation cognitive doivent être combinés à une prescription mesurée de psychotropes pour aboutir à une meilleure qualité de vie de ces patients.

The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22. 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). The inheritance of the syndrome (10%) is autosomal dominant. Most people with 22q11.2DS are missing a sequence of about 3 million DNA building blocks (base pairs) on one copy of chromosome 22 in each cell. A small percentage of affected individuals have shorter deletions in the same region (contiguous gene deletion syndrome). The general features of 22q11.2DS vary widely (more than 180 phenotypic presentations) and the syndrome is under diagnosed. Characteristic symptoms may include congenital heart disease, defects in the palate, neuromuscular problems, velo-pharyngeal insufficiency, hypoparathyroidism, craniofacial features and problems with the immune system T-cell mediated response (caused by hypoplasia of the thymus).

The neurocognitive phenotype of the 22q11.2DS is complex. Cognitive deficits are seen in the majority (80–100%) of individuals with 22q11DS with impairments in sustained attention, executive function, memory and visual-spatial perception. Borderline intellectual function (IQ: 70–75) is most common, mild intellectual disability (IQ: 55–75) is slightly less frequent and a small percentage of children fall into the low average intelligence range. Most children with 22q11.2DS achieve higher scores in verbal tasks than in non-verbal tasks, although this pattern of dysfunction being not universal. Brain MRI studies have shown volumetric changes in multiple cortical and subcortical regions in individuals with 22q11DS that could be related to both cognition and psychoses.

General psychiatric features included anxiety disorders, attention deficit disorder and poor social skills (40–50%). An elevated risk of bipolar disorder and major depression occurs in adolescence and young adulthood. A strong and specific relationship exists between the presence of the 22q11.2 microdeletion and schizophrenia (30–40%). This risk is not associated with any other neurogenetic syndrome. Social cognition is impaired in 22q11.2 DS and this observation is correlated with psychotic features. So, long-term medical care is increasingly being directed towards the treatment and recognition of these symptoms.

Required pharmacological treatment strategies have to be adapted to the syndrome. Moreover, cognitive remediation is a promising tool for treating neuro- and social cognitive deficits in 22q11.2DS. However, these new therapeutic strategies have to be developed to improve quality of life.