Trinucleotide repeat disorders in pediatrics

The relationship between the expansion of trinucleotide repeat sequences and human disease hs been the subject of a significant volume of study since the identification of a CGG repeat sequence in the mutated gene responsible for the fragile X syndrome. Six other neurologic diseases are now known to result from a triplet repeat expansion of either CTG or CAG nucleotides. Of particular interest to the pediatrician or pediatric subspecialist is the phenomenon of "anticipation," now clarified by mechanisms inherent to trinucleotide repeat expansions. The progressive enlargement of repeat sequences in successive generations of affected kindreds correlates inversely with the age of onset and, in some cases, the severity of the disease. The presentation of a young patient with symptoms ranging from developmental delay to movement disorders and ataxia requires that the physician involved in the child's care be aware of these diseases, their phenotypic variability, and their effects in previous generations. In this manner, pertinent history, including family history, may be obtained, relevant diagnostic testing initiated, and appropriate referrals facilitated.