Review Question - QID 106975

The boy is presenting with Fragile X syndrome characterized by a trinucleotide of CGG on the sex X chromosome.

Fragile X syndrome is an X-linked trinucleotide repeat expansion disorder of CGG and may show anticipation, but there may not always be a history of family disease. On physical exam, the behavioral symptoms present as the following: delay in movement such as crawling or rolling, hand-clapping and/or hand-biting, hyperactive or impulsive behavior, mental retardation, speech and language developmental delay, avoidance of eye contact, and autism spectrum disorder. The physical signs include flattened feet, flexible joints, low muscle tone, enlarged body habitus, enlarged, elongated foreheads, long face, low-set or large protruding ears, pectus excavitatum, soft skin, and macroorchidism.

Wattendorf and Muenke review Fragile X syndrome. Management of Fragile X syndrome is typically supportive, focusing on measures to reduce stress/anxiety and behavioral therapy. For the psychiatric manifestations of the disorder, medications are often sufficient.

Penagarikano et al. reviews in greater detail the pathophysiology of Fragile X syndrome. The expansion of CGG in the 5' UTR region of the FMR1 gene results in the hypermethylation and consequent silencing of the expression of the gene. It is thus the absence of the FMR1 gene that produces the phenotype. FMR's functions as a negative regulator of translation and plays a role in synaptic plasticity by regulating the synthesis of proteins located in the dendrite.

Illustration A demonstrates a young boy with Fragile X syndrome. Notice the large protruding, long thin face, and large jaw.

Incorrect Answers:
Answer 1: Huntington's diseases is due to a trinucleotide repeat expansion of CAG.
Answer 3: Freidrich ataxia is due to a trinucleotide repeat expansion of GAA.
Answer 4: Myotonic dystrophy type 1 is due to a trinucleotide repeat expansion of CTG.
Answer 5: Spinal and bulbar muscular atrophy is due to a trinucleotide repeat expansion of CAG. It differs from Huntington's in that the expansion occurs in the sex X chromosome and Huntington's occurs on chromosome 4.