Are some multiple congenital anomalies with mental retardation (MCA/MR) the clinical expression of rare autosomal fragile sites?

A boy with MCA/MR and a fragile site (FS) at 8q22 opens the discussion of a possible association between a rare autosomal FS and an abnormal phenotype. The child was born after prenatal diagnosis of ureterohydronephrosis. He had facial dysmorphia and mental retardation (IQ = 40). The karyotype showed 8q22 FS in 12% of the cells obtained after addition of FUdR to the culture medium. No other etiologic factor was shown to be responsible for the MCA/MR syndrome. Several authors have reported a variety of neurodevelopmental abnormalities and mental retardation in individuals with rare FS expressed on chromosomes 2, 9, 10, 16 and 19. If rare FS predispose to phenotypic abnormalities what are the mechanisms?