Terms in this set (61)

*****Key Points in Fragile X
1. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. The prevalence in females is x of that in males
2. FXS is an X-linked disorder. It is caused by a loss of function mutation in the fragile X mental retardation 1 (FMR1) gene that leads to decreased or absent fragile X mental retardation protein. This gene is normally comprised of x or fewer cytosine-guanine-guanine repeats. The premutation consists of x to x CGG repeats and the full mutation contains over x repeats.
3. Elongation of the CGG repeats leads to x, x, and reduced production of the fragile X mental retardation protein
4. Sherman paradox
5. Fragile X syndrome is associated with a variety of physical, behavioral, and cognitive abnormalities that vary according to the patient's age, sex, and degree of CGG elongation.
6. Classic physical features include long and narrow face with prominent forehead and chin, large ears, and testicular enlargement, but these features are typically not obvious until adolescence or adulthood. Physical features in younger males may include macrocephaly, stabismus, midface hypoplasia, arched palate, mitral prolapse, hyperextensible joints, hypotonia, soft skin, and flexible flat feet.
7. Intellectual disability is usually in the moderate range, expressive language is x affected than receptive language
8. Behavioral features include hyperactivity, inattention, gaze aversion, stereotypic movements (hand flapping, hand biting), hyperarousal, social anxiety, and unusual speech
9. Girls with the full mutation usually have milder features than boys, and x% have normal cognitive function
10. How to diagnose FXS?
11. Following initial diagnosis of FXS, children and adolescents should undergo a multidisciplinary eval for educational planning, assessment of behavioral and emotional needs, and associated medical problems (Gastroesophageal reflux, hypotonia, joint laxity, mitral valve prolapse, seizures, strabismus, recurrent otitis media, scoliosis)
12. Preconception or prenatal screening for the fragile X mental retardation 1 gene should be offered to individuals seeking reproductive counseling who have a family history of fragile X syndrome. Women with a family history of undiagnosed intellectual disability should also be offered carrier screening.
13. Prenatal diagnosis of potentially affected fetuses should be offered in pregnancies in which the mother possesses a premutation or full mutation.
*****Key Points in Fragile X
1. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. The prevalence in females is 50% of that in males
2. FXS is an X-linked disorder. It is caused by a loss of function mutation in the fragile X mental retardation 1 (FMR1) gene that leads to decreased or absent fragile X mental retardation protein. This gene is normally comprised of 40 or fewer cytosine-guanine-guanine repeats. The premutation consists of 61 to 200 CGG repeats and the full mutation contains over 200 repeats.
3. Elongation of the CGG repeats leads to hypermethylation, impaired translation, and reduced production of the fragile X mental retardation protein
4. Sherman paradox - indicates that the variatino in the propensity of premutations to become full mutations may be related to the size of a permutation and the gender of the carrier.
5. Fragile X syndrome is associated with a variety of physical, behavioral, and cognitive abnormalities that vary according to the patient's age, sex, and degree of CGG elongation.
6. Classic physical features include long and narrow face with prominent forehead and chin, large ears, and testicular enlargement, but these features are typically not obvious until adolescence or adulthood. Physical features in younger males may include macrocephaly, stabismus, midface hypoplasia, arched palate, mitral prolapse, hyperextensible joints, hypotonia, soft skin, and flexible flat feet.
7. Intellectual disability is usually in the moderate range, expressive language is x affected than receptive language
8. Behavioral features include hyperactivity, inattention, gaze aversion, stereotypic movements (hand flapping, hand biting), hyperarousal, social anxiety, and unusual speech
9. Girls with the full mutation usually have milder features than boys, and 50% have normal cognitive function
10. How to diagnose FXS? PCR and Southern blot
11. Following initial diagnosis of FXS, children and adolescents should undergo a multidisciplinary eval for educational planning, assessment of behavioral and emotional needs, and associated medical problems (Gastroesophageal reflux, hypotonia, joint laxity, mitral valve prolapse, seizures, strabismus, recurrent otitis media, scoliosis)
12. Preconception or prenatal screening for the fragile X mental retardation 1 gene should be offered to individuals seeking reproductive counseling who have a family history of fragile X syndrome. Women with a family history of undiagnosed intellectual disability should also be offered carrier screening.
13. Prenatal diagnosis of potentially affected fetuses should be offered in pregnancies in which the mother possesses a premutation or full mutation.