A mentally retarded 14-year-old boy has a long face, large ears, micropenis, and large testes. Chromosome analysis is likely to demonstrate which of the following?
The physical features associated with the fragile X syndrome become more obvious after pubey. They include a long face, large ears, prominent jaw, macroorchidism, hypotonia, repetitive speech, gaze avoidance, and hand flapping. Even in the absence of physical findings, boys of all ages with developmental delay, autism, and abnormal temperament of unknown cause probably should be tested for the fragile X syndrome. The genetics of the fragile X syndrome are unique. Most males who carry the fragile X mutation are mentally impaired and show the clinical phenotype; however, 20% of males who inherit the genetic mutation are normal in intelligence and physical appearance. They are also cytogenetically normal in that the fragile site on their X chromosome is not seen by the karyotyping method. These normal transmitting males (NTMs) transmit the fragile X mental retardation (FMR-1) gene to all of their daughters and often have severely affected grandchildren. It is thought that a premutation carried by these NTMs must go through oogenesis in their daughters to become a full mutation. Daughters of NTMs are usually normal but are obligate carriers of the FMR-1 gene. Daughters who inherit the gene from the mother are mentally retarded about one-third of the time. Because both males and females can be affected, the fragile X syndrome is best described as a dominant X-linked disorder with reduced penetrance in females. Cytogenetic testing for the fragile site on the X chromosome is an unsatisfactory method of identifying persons with this mutation for the following reasons: (1) not all cells in the affected males show the fragile site, (2) NTMs have no fragile X site demonstrable by this method, and (3) a significant percentage of carrier females are cytogenetically normal. In 1991, the FMR-1 gene was cloned. Direct DNA analysis is now available for diagnosis of phenotypically affected persons as well as suspected carriers of fragile X; it can also
Trisomy 21
Trisomy 18
Trisomy 13
Fragile X syndrome