Phenotypic variation in male-transmitted fragile X: genetic inferences

Three families with confirmed and one family with suspected male transmission of the fragile X are presented, with psychological and physical assessment of all available members. The psychological tests used were the Peabody Picture Vocabulary test and Block Design which measured verbal and non-verbal abilities, respectively. Physical status was assessed by recording dysmorphic features and by anthropometric measurements. This study demonstrated that there are appreciable differences in mental and physical status within sibships of daughters of male carriers, as well as recognizable physical alterations and intellectual impairment in the transmitting males. These findings contradict the concept that there are two distinct categories of fragile X carriers: phenotypically normal as opposed to affected. They suggest instead that the defect may be graded and emphasize the importance of intellectual deficits and physical alterations in defining the fragile X phenotype, both in low-penetrant males and female heterozygotes.