Fragile X Syndrome

 

Ms. Sneha R. Dubey,  Mr.Hanokh J.Chakranarayan

Suretech College of Nursing, Nagpur

 

ABSTRACT:

Fragile X syndrome, also known as FXS, is a genetic disorder, which causes a wide range of problems, from learning disabilities or attention deficits to more significant developmental delays or mental retardation. Fragile X syndrome also can cause significant emotional or behavioral problems, including anxiety, panic attacks, and hyperactivity or Attention Deficit Hyperactivity Disorder (ADHD). Fragile X syndrome is the most common cause of inherited mental retardation. Where the X chromosome is viewed under the microscope, it narrows at the site of the mutation. This narrowing makes the X chromosome look fragile, as if it would break, hence the name, fragile X syndrome.

 

 

 

INTRODUCTION:

Definition:

Is an inherited genetic disorder disease passed down from parents to children that causes intellectual and developmental disabilities is also known as Martin-Bell Syndrome

 

What causes fragile X syndrome:

Fragile X syndrome is caused by a mutation in the Fragile X Mental Retardation 1 gene (FMR1), which is located on the bottom end of the X chromosome. The FMR1 gene produces a protein that is important for normal brain development.

 

 

 

 

 

FIG .I

 

The full mutation undergoes a process of methylation, whereby a methyl group (CH3) is placed on the backbone of the DNA, and the gene is "turned off." Because the gene is turned off, the protein it usually makes is not made. It is the absence-or a deficiency-of the FMR1 protein that causes fragile X syndrome.

 

The permutation (50 to 200 CGG repeats) and other cells with the full mutation (greater than 200 CGG repeats), so they produce a limited amount of protein, and may be less affected than those individuals who have a full mutation.

 

 

Who gets fragile X syndrome:

Boys are more often affected by fragile X syndrome, because they have only one X chromosome. Their other sex chromosome is Y, which makes them male. If they have a full mutation on their X chromosome, they will be significantly affected by fragile X syndrome.

 

Girls, on the other hand, have two X chromosomes. If a full mutation occurs on only one of them, then their other X chromosome will produce some FMR1 protein, if not a full amount. Thus, they will be less affected, as compared to males

 

Usually, girls with the full mutation have learning disabilities or attention deficit problems; although, in approximately 70% of cases, their IQ will be either in the borderline range (70 to 85) or in the mildly retarded range (50 to 69).Both males and females can be carriers of this disorder with the permutation.

 

Fragile X syndrome usually affects multiple individuals in a family tree; therefore, genetic counseling is important. A genetic counselor will review the problems of all individuals in an extended family, and will talk with family members who are at risk of being a carrier or affected by this disorder.

 

How does a FMR1 mutation cause disease:

The FMR1 mutation causes disease because the CGG expansion in the full mutation range will turn off the gene, which, in turn, prevents the production of the FMR1 protein.

 

What are the common findings:

 Children with fragile X syndrome have language delays, i.e., they may not speak in phrases or sentences by 2 or 2 years of age.

 

They also may be hyperactive, inattentive, or impulsive early in childhood, which can lead to a diagnosis of ADHD.

 

Children with FXS are usually extra sensitive to stimuli in their environment, and they frequently have tantrums or emotional outbursts in crowded situations or when making a transition between activities.

 

Shyness or social anxiety may be a common problem; however, initially, many individuals may be shy, and, subsequently, they become impulsive or talkative in social interactions.

 

Children with FXS have changes in their connective tissue, such as soft skin, "double-jointed" fingers and thumbs, prominent ears, or a long face.

 

Large testicles are commonly seen in boys with fragile X syndrome; however, this only begins to occur in adolescence or just before the onset of puberty. Many children may be diagnosed with autistic-like features, such as hand flapping, hand biting, poor eye contact, repetitive speech, and sensitivity to being touched.

 

Rarely, individuals with FXS may have hernias or joint dislocations. Recurrent vomiting is a common problem at the time of birth, and, occasionally, may persist into childhood. Seizures may occur in approximately 20% of patients. Typically, seizures start in early childhood, are usually easily controlled with medication, and often disappear by adolescence or adulthood. Eye problems may be seen in up to 50% of children, including a lazy eye or a need for glasses.

 

How is fragile X syndrome diagnosed:

 

FIG.II

 

Fragile X syndrome can be diagnosed by two methods; both involve a blood test.

 

The first method is called cytogenetic testing. The white blood cells are grown in a lab to show the fragile site on the bottom end of the X chromosome. Not every individual affected by FXS will show the fragile site on the X chromosome.

 

The second method is called FMR1 DNA testing. DNA testing will demonstrate the CGG repeat number at the FMR1 gene. This test will diagnose all individuals affected by fragile X syndrome. It also will identify those individuals who are carriers, which cytogenetic testing does not.

 

Your doctor can order DNA testing or cytogenetic testing on your child, but all individuals who are suspected of having the Fragile X chromosome should have a DNA test, even if cytogenetic testing was previously performed.

 

Rarely, an individual who is positive on cytogenetic testing may be negative on DNA testing, meaning they do not have a mutation at the FMR1 gene

 

How is fragile X syndrome treated:

All individuals who are affected by FXS require speech and language therapy and occupational therapy, usually with a sensory integration approach. These therapies stimulate and improve motor and language development.

In children who have more severe motor problems, treatment by a physical therapist also is necessary. Children with FXS often have difficulty with math and, sometimes, spelling and reading. Most children can be mainstreamed into a regular classroom;

 

The use of stimulant medication, such as methylphenidate (Ritalin) and dextroamphetamine (Dexedrine or Adderall), are helpful for the majority of children with FXS who have significant hyperactivity, short attention spans, or impulsive behavior. Usually, these medications are tried at 5 years of age or older; although, occasionally, they can be helpful in the preschool period. Clonidine or guanfacine (Tenex) are medications that can reduce hyperactivity or overstimulation and improve tantrum behavior. These medications can be used after age 3 and, sometimes, can be combined with stimulant medication.

 

The Selective Serotonin Reuptake Inhibitors (SSRIs), such as Prozac, Zoloft, Paxil, or Luvox, can be helpful in treating anxiety, panic attacks, obsessive compulsive behavior, or aggression and outburst behavior.

 

These medications can be used in childhood, adolescence, or adulthood. Sometimes, severe behavioral problems may require the use of an atypical anti-psychotic drug, such as risperidone; however, such a drug should be used in low doses. These require the use of either preventive antibiotics or pressure equalizing tubes to ensure that hearing is normalized and not damaged by continued infections.

 

Siblings of a child with FXS should be tested for it with FMR1 DNA testing. Genetic counseling is available to guide prenatal diagnostic procedures, which can identify the degree of the mutation of the fetus at approximately 10 to 15 weeks of pregnancy.

 

What are the complications:

The complications of treating FXS include side effects from the medications that are used. Higher doses of stimulant medication can cause weight loss, sleep disturbances, or high blood pressure.

 

Children who are treated with medications should see their physicians at least 2 to 3 times per year to follow growth parameters and blood pressure. Medications, such as clonidine or guanfacine, can cause significant sedation, and also may require an EKG.

 

The SSRIs can cause gastrointestinal disturbances or diarrhea, which can be improved by adjusting the dosage or changing to a different medication. Careful follow-up with us about side effects can lead to medication changes and improved symptom.

 

How is fragile X syndrome prevented:

It is possible to perform prenatal diagnostic testing for FXS using the FMR1 DNA test.

 

 

Such decisions regarding termination or carrying on a pregnancy with a fetus affected with FXS are very personal decisions. The family must make the decision that is right for them. The genetic counselor and the physician will be supportive of the family's decision.

 

CONCLUSION:

Is an inherited genetic disorder disease passed down from parents to children that causes intellectual and developmental disabilities is also known as Martin-Bell Syndrome. Fragile X syndrome is the most common cause of inherited mental retardation. Where the X chromosome is viewed under the microscope, it narrows at the site of the mutation. This narrowing makes the X chromosome look fragile, as if it would break, hence the name, fragile X syndrome.

 

ACKNOLOGEMENT:

I would like to thanks to my parents, mrs.Mercy Anjore (vice principal HOD-OBG Department Suretech College of nursing).

 

REFERENCES:

1.       Hagerman, Randi J., and Paul J. Hagerman. Fragile X syndrome: diagnosis, treatment, and research. 3, illustrated ed. Baltimore, MD: JHU P, 2002

2.       Pietropaolo S; Guilleminot A; Martin B; D'Amato FR; Crusio WE (2011). "Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice". PLOS ONE. 6 (2): e17073. Bibcode:2011PLoSO...617073P. doi:10.1371/journal.pone.0017073. PMC 3043074 . PMID 21364941.

3.       Spencer CM, Graham DF, Yuva-Paylor LA, Nelson DL, Paylor R (June 2008). "Social behavior in Fmr1 knockout mice carrying a human FMR1 transgene". Behavioral Neuroscience. 122 (3): 710–715. doi:10.1037/0735-7044.122.3.710. PMID 18513141.

4.       Berry-Kravis, E; Raspa M, Loggin-Hester L, Bishop E, Holiday D, Bailey Jr DB. (2010). "Seizures in Fragile X Syndrome: Characteristics and Comorbid Diagnoses". Am J Intellect Dev Disabil. 115 (6): 461–72. doi:10.1352/1944-7558-115.6.461. PMID 20945999.

5.       Bernardet M; Crusio WE (2006). "Fmr1 KO mice as a possible model of autistic features". TheScientificWorldJournal. 6: 1164–1176. doi:10.1100/tsw.2006.220. PMID 16998604.

6.       Bibi G; Malcov M; Yuval Y; Reches, Adi; Ben-Yosef, Dalit; Almog, Beni; Amit, Ami; Azem, Foad (May 2009). "The effect of CGG repeat number on ovarian response among fragile X premutation carriers undergoing preimplantation genetic diagnosis". Fertil. Steril. 94 (3): 869–74.

7.       Dobyns, William B.; Filauro, Allison; Tomson, Brett N.; Chan, April S.; Ho, Allen W.; Ting, Nicholas T.; Oosterwijk, Jan C.; Ober, Carole (2004). "Inheritance of most X-linked traits is not dominant or recessive, just X-linked". American Journal of Medical Genetics. 129A (2): 136–43.

8.       Rueda, JR; Ballesteros, J; Guillen, V; Tejada, MI; Solà, I (11 May 2011). "Folic acid for fragile X syndrome". The Cochrane Database of Systematic Reviews (5): CD008476. doi:10.1002/14651858.CD008476.pub2. PMID 21563169.

 

 

 

 

Received on 08.08.2018       Modified on 06.09.2018

Accepted on 05.10.2018       ©A&V Publications All right reserved