Le syndrome vélo-cardio-facial (délétion 22q11.2): une revue de littérature et présentation d'un cas clinique

Abstract

Velocardiofacial syndrome (VCFS) is estimated to occur in at least one per 2000-4500 births. The characteristic features of the disorder are hypernasal speech, cardiac defects, a distinctive facial appearance, learning disabilities and behavioural disturbances. More than 100 congenital medical conditions or physical abnormalities are associated with velocardiofacial syndrome, however, there is great variability in the frequency and severity of the associated problems. The objective of this study is to describe velocardiofacial syndrome and provide an illustrative case study as a way of understanding how a neurogenetic syndrome specifically affects physical, cognitive and behavioural development. In 1992, Scambler et al. identified a common microdeletion at chromosome 22q11.2 in patients affected by velocardiofacial syndrome and other similar syndromes known at that time by different names. Individuals with the 22q11.2 deletion are hemizygous for all genes contained by the deletion site. In most affected individuals, a de novo 3 mb deletion at chromosome 22q11.2 is responsible for the syndrome; however, in 10-25% of cases, velocardiofacial syndrome is inherited from a parent with velocardiofacial syndrome. At least 30 genes are encoded in the commonly deleted segment, a few of which are highly expressed in brain tissue and likely to be essential for normal brain development. Certain specific genes within the 22q11.2 deletion site have attracted intense interest because of their known relationship to central nervous system structure or functioning (GSCL, Es2, UFD1L, COMT, TBX1). Over the past decade, MRI methodologies have been utilised to investigate the effect of the 22q11.2 deletion on brain structure. The majority of the available neuroimaging literature suggests early alterations of the parietal lobe and cerebellum. Furthermore, recent studies report significant structural changes in cerebral morphology. As much as an 11% reduction in total brain volume, including grey and white matter, has been reported. Notably, the areas most significantly decreased in size were parietal lobe grey matter in the left hemisphere, the cerebellum and the vermis. Moreover, an accelerated decrease, increasing in rate as a function of age, of grey matter in the temporal lobes and hippocampus has been found in affected individuals during childhood and adolescence. Most of the brain alterations described in velocardiofacial syndrome are common to those reported in the neuroimaging literature on schizophrenia. In patients with adult-onset schizophrenia, substantial grey-matter volume reduction is evident at the first clinical presentation of the disorder. The majority of toddler and preschool children with velocardiofacial syndrome have mild gross motor delays and severe expressive and receptive language delays. By school age children and adolescents with velocardiofacial syndrome demonstrate mild to moderate decrements in overall cognitive and language abilities. Some learning disabilities are almost invariably present. The cognitive profile of velocardiofacial syndrome is generally characterised by non-verbal deficits. It has been suggested that they might have lower non-verbal IQ than verbal IQ scores. Children with this disease also have a high rate of maladaptive behaviours and social problems including: impulsive, emotionally labile and disorganised behaviours, and social problems such as shyness or disinhibition. Psychiatric disorders have frequently been reported in individuals with this syndrome. Multiple studies have suggested that approximately 20-30% of people with velocardiofacial syndrome develop schizophrenia, establishing velocardiofacial syndrome as the first identified genetic subtype of schizophrenia. In summary, in the current report we describe the genetic, medical, cognitive and psychiatric aspects of velocardiofacial syndrome from infancy to adulthood.