Recommendations from Multi‐disciplinary Focus Groups on Cascade Testing and Genetic Counseling for Fragile X‐associated Disorders

McConkie‐Rosell, Allyn; Abrams, Liane; Finucane, Brenda; Cronister, Amy; Gane, Louise W.; Coffey, Sarah M.; Sherman, Stephanie L.; Nelson, Lawrence M.; Berry‐Kravis, Elizabeth; Hessl, David; Chiu, Sufen; Street, Natalie; Vatave, Ajay; Hagerman, Randi J.

doi:10.1007/s10897-007-9099-y

Cited by 73 publications

(59 citation statements)

References 58 publications

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“…40 The presence in the proband's family of movement disorders, learning disabilities, mental retardation, or primary ovarian insufficiency should increase suspicion of the presence of FMR1 mutations in the family. 41 A suggested targeted family history questionnaire can be found in Table 2. The testing procedure encompasses two complementary analyses.…”

Section: Diagnostic Approachesmentioning

confidence: 99%

Fragile X syndrome

2008

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In association withFragile X syndrome Fragile X syndrome, an X-linked dominant disorder with reduced penetrance, is associated with intellectual and emotional disabilities ranging from learning problems to mental retardation, and mood instability to autism. It is most often caused by the transcriptional silencing of the FMR1 gene, due to an expansion of a CGG repeat found in the 5 0 -untranslated region. The FMR1 gene product, FMRP, is a selective RNA-binding protein that negatively regulates local protein synthesis in neuronal dendrites. In its absence, the transcripts normally regulated by FMRP are over translated. The resulting over abundance of certain proteins results in reduced synaptic strength due to AMPA receptor trafficking abnormalities that lead, at least in part, to the fragile X phenotype.

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Section: Diagnostic Approachesmentioning

confidence: 99%

Fragile X syndrome

2008

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“…McConkie-Rosell et al (2007) have highlighted the need to develop information materials such as targeted brochures and fact sheets to increase women's understanding of risks and benefits at the time of offering screening that should be based on appropriate pre-test and post-test counselling guidelines (Archibald et al 2009). …”

Section: Carrier Screening For Fragile X Syndromementioning

confidence: 99%

Carrier screening in preconception consultation in primary care

Metcalfe

2011

J Community Genet

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Discussing carrier screening during preconception consultation in primary care has a number of advantages in terms of promoting autonomy and enabling the greatest range of reproductive choices. For those with a family history of an inherited condition, this ought to be a routine discussion; however, this can be expanded to include the wider population, especially for those conditions for which carrier frequencies are considered relatively common. There is published literature from around the world regarding experiences with carrier screening in primary care for cystic fibrosis, haemoglobinopathies, fragile X syndrome, Tay-Sachs disease and spinal muscular atrophy, although many of these have tended to focus on consultations during rather than before pregnancy. Overall, these studies reveal that population carrier screening is well received by the participants with apparent minimal psychosocial harms; however, challenges exist in terms of approaches to ensure couples receive adequate information to make personally relevant decisions and for ongoing health professional engagement.

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“…68 McConkie-Rossell et al 52 have also highlighted the need to develop information materials such as targeted brochures and fact sheets to increase women's understanding of risks and benefits at the time of offering screening. As part of developing and testing educational and counseling strategies, consideration should be given to the different ways carrier screening for FXS could be offered within a particular setting.…”

Section: Carrier Screening For Fxs In Women Of Reproductive Agementioning

confidence: 99%

“…In these cases, the FMR1 gene is switched off as a result of an increase in the number of hypermethylated trinucleotide (CGG) repeats in the 5Ј untranslated region of the gene. Current definitions describe the normal range of CGG repeats as 6 -44, the "gray zone" range as [45][46][47][48][49][50][51][52][53][54] repeats, and the premutation range as 55-199 repeats. 8 Those affected by FXS have Ͼ200 repeats (full mutation).…”

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A systematic review of population screening for fragile X syndrome

Hill

Archibald

Cohen

et al. 2010

Genetics in Medicine

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Purpose: To conduct a systematic review of literature regarding population-based screening for fragile X syndrome in newborns and women of reproductive age, either before or during pregnancy. Methods: Seven electronic databases were searched for English language studies published between January 1991 and November 2009. Data extraction was performed for all included studies. Results were synthesized using a narrative approach. Results: One article that examined offering newborn screening for fragile X syndrome and 10 that examined the offer of fragile X syndrome screening to women of reproductive age were identified. Two of these articles also addressed psychosocial aspects of population screening for fragile X syndrome such as attitudes to screening and experiences of screening, and a further nine addressed these issues alone. Studies exploring psychosocial issues demonstrated challenges for counseling arising from a lack of awareness or personal experience with fragile X syndrome in the general population. Conclusions: Targeted counseling and educational strategies will be essential to support women from the general population. It is crucial that future studies offering screening for fragile X syndrome explore a range of psychosocial aspects in addition to looking at uptake of testing and mutation frequency. Genet Med 2010:12(7):396 -410.Key Words: attitudes, carrier screening, fragile X syndrome, newborn screening, psychosocial P opulation-based screening programs for a number of genetic conditions have been established in newborn, prenatal, and preconception settings. Specific criteria, such as those developed by the World Health Organization, 1,2 are available to provide guidance on which conditions are suitable for screening. 3 Fragile X syndrome (FXS) is an X-linked genetic condition for which possible inclusion in population-based screening programs has been discussed and debated for many years. 4 -7 FXS is the most common known cause of inherited intellectual and developmental disability. It has a serious adverse impact on individuals and their families that is equivalent to that of other disabilities such as Down syndrome and autism. Most FXS cases are caused by the silencing of the FMR1 gene, which is located on the X chromosome. In these cases, the FMR1 gene is switched off as a result of an increase in the number of hypermethylated trinucleotide (CGG) repeats in the 5Ј untranslated region of the gene. Current definitions describe the normal range of CGG repeats as 6 -44, the "gray zone" range as 45-54 repeats, and the premutation range as 55-199 repeats. 8 Those affected by FXS have Ͼ200 repeats (full mutation). The length of the CGG repeat is unstable over a certain size, such that a premutation can expand to a full mutation when passed onto offspring through female, but not male, premutation carriers. 9 -11 Similarly, a gray zone allele can increase to a premutation allele when transmitted to offspring, such that a grandchild could be affected with FXS.The full mutation is associated with intell...

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Recommendations from Multi‐disciplinary Focus Groups on Cascade Testing and Genetic Counseling for Fragile X‐associated Disorders

Cited by 73 publications

References 58 publications

Fragile X syndrome

Fragile X syndrome

Carrier screening in preconception consultation in primary care

A systematic review of population screening for fragile X syndrome

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