FRAGILE X SYNDROME

Disease

Brief Summary

The Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. FXS is caused by changes in a gene called the fragile X mental retardation 1 (FMR1) gene. The FMR1 gene usually makes a protein called fragile X mental retardation protein (FMRP). FMRP is needed for normal brain development. People who have FXS do not make this protein.

Source

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People affected by Fragile X Syndrome

Frequency

The fragile X syndrome affects about 1 in 4,000 males and 1 in 6,000 to 8,000 females in the USA. The Philippines, with a population of over 104 million people, is believed to have over 10,000 people with Fragile X syndrome and many more who are carriers.

Inheritance

The fragile X syndrome is inherited in a X-linked dominant manner.

History of Disease

The X-linked mental retardation reported by Martin and Bell (1943) is the same as the fragile X syndrome. The disorder was first referred to as the 'Martin-Bell syndrome' on the assumption that the family reported from the Queen Square Hospital in London by J. Purdon Martin and Julia Bell (Martin and Bell, 1943) had that disorder. Although macroorchidism was not mentioned by Martin and Bell (1943), one of the patients was described as having a 'big face and jaw;' furthermore, at least 9 of the affected males were maternal grandsons of 2 unaffected brothers.

Brief Summary

History of Disease

Pathogenesis

Achondroplasia is caused by a mutation in the FGF3 gene in chromosome 4 at 4p 16.3. This mutation causes a decreased production of fibroblast growth factor receptor 3 which is crucial in the conversion of cartilage into bone which is vital in the proper development of a person. This mutation is inherited in an autosomal dominant manner. More than 80 percent of people with achondroplasia have parents with normal characteristics and are born with achondroplasia due to a recent (de novo) gene modification (mutation).

Pathogenesis

Fragile X Syndrome (FXS) is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes.

There is a place in the FMR1 gene where the DNA pattern CGG is repeated over and over again. In most people, the number of repeats is small (5 to 44 repeats), which is normal. Having more repeats can change how much protein is made, and it increases the risk for associated disorders and related concerns. If the number of repeats is too large (more than 200 repeats), the gene turns off. When the gene is turned off, no protein is made. Without the protein, the person develops FXS. This is called a “trinucleotide repeat disorder.” People get (inherit) the disorder from their parents.

Source

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Mutated chromosome by Fragile X Syndrome

Symptoms

large ears

soft skin

long and narrow face

large testicles (macroorchidism)

flexible joints

delayed speech

delayed motor skills

repetitive and unclear speech

Social Concerns

There are issues about the termination of pregnancy in relation to fragile X syndrome and fragile X tremor ataxia syndrome. Also, carrier testing for fragile X syndrome has potential health implications for the tested individual and could heighten discrepancies in how men and women experience genetic risk or decide about testing.

Treatment

There is no single treatment for Fragile X syndrome, but there are treatments that help minimize the symptoms of the condition. These include educational support and therapy, screening, and treatment for associated medical conditions, and behavioral health treatment. Families may receive genetic counseling, participate in clinical research, and connect with the wider community of people with fragile X syndrome and their family members. Early intervention is also important. Because a young child’s brain is still forming, early intervention gives children the best start possible and the greatest chance of developing a full range of skills.

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Treatment for Fragile X Syndrome

Clinical Trials

Title:

Combined Treatment of Minocycline and Lovastatin to Treat Individuals With Fragile X Syndrome (LovaMiX)

Intervention:

(A) Drug: Minocycline, then Minocycline/Lovastatin

(B) Drug: Lovastatin, then Minocycline/Lovastatin

Phase:

Phase 2

Procedure:

(A) 1. One tablet of 50mg minocycline will be taken daily by participants for four weeks.

2. After the initial four weeks, One tablet of 100mg minocycline will be taken daily by participants for the succeeding four weeks.

3. A combined treatment of minocycline 100 mg and lovastatin 40mg will follow for the next 12 weeks.

(B) 1. Participants of this group will take 1 tablet of lovastatin 20 mg daily for 4 weeks.

2. One tablet of 40mg lovastin will be taken for another four weeks;

3. Finally, a combined treatment of minocycline 100 mg and lovastatin 40 mg for the following 12 weeks.

Goal:

The purpose of this study is to determine whether Lovastatin, Minocycline and the combination Lovastatin/Minocycline are effective in treating behavioral symptoms in Fragile X individuals.

Further details at:

This study is referred to as NCT02680379 in the Information from the National Library of Medicine website. You may also go to this link to learn more about the details of the clinical trial.

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