Review Question - QID 106507

Given the patient's characteristic physical features of a long face, protruding ears, male sex, and learning disability, he likely has Fragile X syndrome. Following puberty, these individuals characteristically have macroorchidism.

Fragile X is caused by CGG trinucleotide expansion within the FMR1 gene located on the X chromosome. Affected individuals have characteristic physical features such as macrocephaly, a large jaw, frontal bossing, and macroorchidism following puberty. Additionally, affected individuals may also exhibit strabismus, connective tissue dysplasia including mitral valve prolapse and hyper-extensible joints. They may also exhibit specific behaviors such as attention deficit, hand flapping, hand biting, and averting one's gaze. Most affected males have mild to severe mental retardation.

Wattendorf and Muenke discuss the diagnosis of Fragile X syndrome in their review. As the physical characteristics of Fragile X syndrome may be subtle during early childhood, the average age of diagnosis is 8 years old. Typically the initial findings are delayed attainment of developmental milestones. Diagnosis is confirmed with molecular genetic testing of the FMR1 gene. A full mutation has greater 200 repeats and is also hypermethylated. This leads to an inability to produce the FMR1 gene.

Picker and Walsh discuss potential new therapies for treating those with intellectual disability, such as that caused by Fragile X syndrome. The FMR1 gene regulates dendritic growth, and the absence of the protein leads to disordered growth. Experiments using GABA agonists have shown modest improvements in social function and behavior.

Figure A demonstrates a young boy with the characteristic findings of Fragile X syndrome, including protruding ears and a large jaw. Illustration A demonstrates the typical appearance of a Fragile X chromosome following karyotyping. The multiple repeats make the chromosome susceptible to breakage during preparation.

Incorrect Answers:
Answer 1 and 2: These are characteristic physical findings in Klinefelter syndrome.
Answer 3: Those with Fragile X syndrome tend to exhibit macrocephaly, not microcephaly.
Answer 5: These tumors appear in those with Neurofibromatosis Type I and II, not Fragile X syndrome.