Definition of Fragile X syndrome
1. Noun. A particular, genetic syndrome, caused by the excessive repetition of a particular trinucleotide. ¹
¹ Source: wiktionary.com
Medical Definition of Fragile X syndrome
1.
most frequent cause of mental retardation. There is an expanded trinucleotide repeat CGG in the fra(X) gene. There is usually a constricted section on the long arm of the X chromosome.
After puberty these patients often exhibit large prominent ears, long narrow face, coarse facial features and macroorchidism. Mental retardation in males is characteristic although the manifestations of the syndrome are highly variable.
A preponderance of males are affected but it also affects 30% of carrier females and about 20% of obligate carrier males are not affected. The complexity in the inheritance pattern comes from the fact that these obligate carrier males (transmitting males) pass on the mutation to all their daughters (unaffected). most of the sons of carrier females with the mutation are mentally retarded but of their daughters, only 1/3 are retarded while 1/3 are borderline retarded and 1/3 are normal.
Penetrance of the disease is variable within families and among siblings. Another unique characteristic of this syndrome, which is referred to as the Sherman Paradox is the fact that the risk of a family member being abnormal when gene-positive depends on the position of the proband in the pedigree.
Sons of phenotypically normal but transmitting males have no risk of being mentally affected, but grandsons and great-grandsons of the transmitting a male have a much higher risk of mental retardation (40% and 50%, respectively). On the other hand, if the carrier female expresses the mental handicap her sons have a 50% risk of mental retardation.
The classical method of confirming diagnosis is culture of lymphocytes in a folate-free medium (or supplemented with trimethoprim, methotrexate or FUdR) and microscopic detection of the fragile site (Xq27.3). Expression is seen in less than 50% of the cells of affected individuals but the test is not applicable to carrier detection as there is a high false negative rate (60%).
The fragile-X gene (FMR-1), which contains tandemly repeated trinucleotide sequences (CGG repeats) on its 5' end, can be detected with PCR or Southern blot techniques. Normal controls show 6-50 CGG repeats, whereas mutation in affected males or heterozygous females can contain as many as 1,000 CGG repeat units.
The test is indicated for individuals with compatible mental retardation, developmental delays or autism, or for those that have a family history of the syndrome. It is also indicated for prenatal detection in offspring of carrier females.
Inheritance: sex-linked.
Incidence: 1 in 1200 males and 1 in 2500 females.
(17 Dec 1997)
Lexicographical Neighbors of Fragile X Syndrome
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