Aetiology of severe mental retardation and further genetic analysis by high-resolution microarray in a population-based series of 6- to 17-year-old children

Aim:  To investigate the prevalence, co-morbidities and aetiologies of severe mental retardation (SMR) in a cohort of Swedish children and to further penetrate aetiologies in the group with undetermined causes by application of updated clinical-genetic methods. Methods:  The study was population-based and included children living in the County of Halland in western Sweden in 2004 (born 1987–1998; 46 000 children). Patients were identified through habilitation centres, paediatric clinics and school health services. Patients with unclear prenatal aetiology were investigated with single nucleotide polymorphism (SNP)-array. Results:  Severe mental retardation was identified in 133 children from 132 families, corresponding to a prevalence of 2.9 per 1000 children. There were more males than females (90:43).The aetiology was prenatal in 82 (62%), perinatal in 14 (10%) and postnatal in 8 (6%). In 29 (22 %) children, mainly males with autism, the cause could not be related to the time of birth. In the prenatal group, genetic causes dominated, but still 23 children remained undiagnosed; in 5/19 of these patients, a diagnosis could be made after SNP-array analysis. One or more associated neurological handicaps were found in more than half of the children. Conclusion:  Prevalence and co-morbidity were similar to previous Scandinavian studies. High-resolution chromosomal micro-array techniques are valuable diagnostic tools, reducing the number of patients with unexplained SMR.