"Familial" versus "sporadic" intellectual disability: contribution of subtelomeric rearrangements

Among the families studied, 27.4% had 4-12, 36.3% had 3 and 36.3% had 2 affected individuals in the first degree relatives. One unbalanced translocation and 4 polymorphic changes were detected. The prevalence of clinically significant subtelomeric rearrangements was 0.98%.This is the first investigation of subtelomeric aberrations in a large sample set of familial ID patients. Our results show that the contribution of subtelomeric rearrangements to familial ID is not as much as what had been determined for sporadic ones in the literature. Moreover, this study shows that the positive family history by alone, cannot be the most important and determining indicator of subtelomeric aberrations while it would be a good predicting factor when associated with dysmorphism or congenital malformations. These findings propose that other cryptic chromosomal abnormalities or even single gene disorders may be the main cause of familial ID rather than subtelomeric aberrations.Intellectual Disability, formerly Mental Retardation, is a lifelong disability with the prevalence of 1-3% that imposes a heavy burden on the society, health care system and affected families. It is defined as having the following components: 1) significantly abnormal intellectual performance determined by IQ tests; 2) onset before the age of 18; 3) impairment of the adaptation to the environment [1]. While the causes of sporadic Intellectual disability (ID) have been thoroughly investigated during recent decades and some new genes causing autosomal recessive ID have been recently reported, [2], still little is known about the underlying genetic causes of familial ID especially in non-recessive types of ID. This could be attributed to the low incidence of familial ID in western countries, where most of the studies have been carried out. Sporadic ID is caused by extremely heterogeneous factors including environmental, chromosomal and monogenic factors. It is estimated that half of all cases of sporadic ID is ca