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Screening for Fragile X Syndrome

ChromosomesToday, the most common inherited form of mental retardation is Fragile X Syndrome. In fact, this has become recognized as being so prevalent that the American College of Obstetrician and Gynecologists (ACOG) recently published a Committee Opinion from the Committee on Genetics regarding Fragile X Syndrome. They pointed out that this disorder has been found to occur in approximately 1 in 4,000 – 6,000 females, and approximately 1 in 3,600 males. In addition, approximately 1 in 250 females carry the permutation for Fragile X, and the syndrome can affect individuals from many different ethnic backgrounds.


With respect to the clinical presentations that are seen in these patients, mental impairment or retardation can range from borderline, including various learning disabilities, to severe, in which patients present with cognitive and/or behavioral disorders, including autism. In fact, Fragile X Syndrome is the most common cause known of autism or “autistic-like” behavior. Most affected males have significant intellectual disabilities, while affected females may have a more subtle presentation (or phenotype), and thus it is at times difficult to establish the diagnosis based solely on clinical findings in female patients. Some of the abnormalities in males include distinctive facial features (such as long, narrow faces and prominent ears), enlarged testicles (macroorchidism), connective tissue problems, and speech and/or language problems. With respect to the facial features, these are subtle and become more pronounced with age, thus clinical diagnosis of this disorder is especially difficult to make in newborn.


Fragile X Syndrome is transmitted genetically as a disorder involving the X chromosome. Unlike many other genetic syndromes, the molecular findings in Fragile X are complex, and based upon the number of abnormal DNA segments (CGG nucleotides) four groups of individuals have been classified:  unaffected, intermediate, permutation, and full mutation. Prenatal testing for Fragile X Syndrome should be offered to known carriers of either the Fragile X permutation, or full mutation. In addition, women with a family history of Fragile X-related disorders, unexplained developmental delay or mental retardation, autism or premature ovarian failure/insufficiency are all candidates for Fragile X screening and genetic counseling as well.


Given the ever-changing realm of reproductive genetics, and new findings that are constantly emerging, it is interesting to note that in this very committee opinion, ACOG points out that “This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed”.

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