The 22q11 deletion syndrome.A clinical and epidemiological study

Abstract: Aims: The aims of this study were to 1) assess the incidence and prevalence of the 22q11 deletion syndrome(22q11DS) in a defined population of western Sweden, 2) to evaluate the presenting phenotype and 3)to investigate the profile of cognitive and nervous system-related disabilities and the resulting handicap,taking into account physical, neurological and psychological aspects.Material and Methods: The incidence was studied in children born in the Western Götaland Region,where Göteborg is the main city, during the years 1991-2000. The prevalence was studied in children inthe region younger than 16 years at the end of the year 2000 (Paper I). The presenting phenotype wasevaluated in a consecutive series of 100 children and adolescents younger than 20 years with the 22q11 DSreferred from the whole of Sweden to the Queen Silvia Children s Hospital in Göteborg during the years1993-2002 (Paper II). Photographs of 80 children were used to evaluate the pattern of characteristic facialfeatures (Paper III). In the first 33 patients older than three years, development, cognition, motor functionand the handicap level according to WHO (1980) were evaluated (Paper IV). All 113 patients included inthe study had 22q11 deletion confirmed by the fluorescence in situ hybridisation test.Results: The mean annual incidence in the whole region was 14.1 per 100,000 live births. During thefirst five years the incidence was higher, 18.1 per 100,000 live births for the whole region and 23.4 per100,000 live births in Göteborg, where a multidisciplinary specialist team for the 22q11DS is based.About 60% had a heart defect and the median age at diagnosis was 0.6 years compared with almost 7years in those without a heart defect. The prevalence was 13.2 per 100,000 children below 16 years ofage in the whole region and 23.3 per 100,000 in Göteborg. The presenting phenotype was studied in100 consecutive children. Twenty-six were diagnosed during infancy and 92% of them had a congenitalheart defect, whereas 54% of those diagnosed later had a cardiac defect. The median age at diagnosis was6.7 years. The typical presentation in those diagnosed early consisted of an association of conotruncalheart defect, hypocalcaemia and hypoplasia of thymus, whereas those diagnosed later most often presentedwith the association of speech-language impairment, developmental delay or learning difficulties andrecurrent infections. A characteristic pattern of mild facial features was noted in children at all ages. Ahigh prevalence of cognitive and other neurologically related impairments was found. Hypotonia, coordinationdisturbance and poor balance were found in most patients. Around two-thirds had definitemotor problems, including two with spastic hemiplegia. Deviant pre-walking locomotion and delayedindependent walking and delayed achievement of bladder control were also common findings. Most hadan IQ below 85, and an IQ below 70 was found in one-third of the children. Performance IQ was moreimpaired than Verbal IQ. As a consequence of these and other associated problems, the resulting handicapwas considerable.Conclusion: The 22q11 deletion syndrome is a common genetic disorder. In spite of variable clinicalexpression, children with the disorder share a number of major features and have a characteristicphenotype. A high proportion has no cardiac defect and hence a diagnostic delay. Increased awareness andknowledge among specialists who meet these children early in life is needed to reduce the diagnostic delay.The comprehensive management of a child with the 22q11DS is challenging because of the wide spectrumand variable expression of impairments and disabilities which, taken together, manifest as a considerablehandicap. A multi-professional approach and an individualised assessment are necessary to give the childadequate treatment and support.