Prevalence and Incidence of Fragile-X Syndrome

Prevalance of Fragile-X Syndrome:

approximately 1 per 8,000 females suffer from fragile X syndrome, Genetics Home Reference website ... see also overview of Fragile-X Syndrome.

Prevalance Rate:

approx 1 in 16,000 or 0.01% or 17,000 people in USA [Source statistic for calcuation: "approximately 1 per 8,000 females suffer from fragile X syndrome, Genetics Home Reference website" -- see also general information about data sources]

Fragile-X Syndrome: Rare Disease

Fragile-X Syndrome is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). This means that Fragile-X Syndrome, or a subtype of Fragile-X Syndrome, affects less than 200,000 people in the US population.

Ophanet, who are a consortium of European partners, currently defines a condition rare when if affects 1 person per 2,000. They list Fragile-X Syndrome as a "rare disease". More information about Fragile-X Syndrome is available from Orphanet

Incidence (annual) of Fragile-X Syndrome:

about 1 in 1500 males¹. ... see also overview of Fragile-X Syndrome.

Incidence Rate:

approx 1 in 3,000 or 0.03% or 90,666 people in USA [Source statistic for calcuation: "about 1 in 1500 males¹." -- see also general information about data sources]

Incidence extrapolations for USA for Fragile-X Syndrome:

90,666 per year, 7,555 per month, 1,743 per week, 248 per day, 10 per hour, 0 per minute, 0 per second. [Source statistic for calculation: "about 1 in 1500 males¹." -- see also general information about data sources]

Prevalence/Incidence of Fragile-X Syndrome: Online Medical Books

16 MEDICAL BOOKS ONLINE! Review excerpts from medical books online, free, without registration, for more information about the prevalence and/or incidence of Fragile-X Syndrome.

Fragile X syndrome: Causes and incidence
(Professional Guide to Diseases (Eighth Edition))

Fragile X syndrome is an X-linked condition that doesn't follow a simple X-linked inheritance pattern. The normal sequence of the FMR1 gene was identified at Xq27.3 in 1991. The unique mutation that results in fragile X syndrome consists of an expanding region of a specific triplet of nitrogenous bases: cytosine, guanine, guanine (CGG) within the gene's deoxyribonucleic acid (DNA) sequence. Normally, FMR1 contains 6 to 50 sequential copies of the CGG triplet. When the number of CGG triplets expands to the range of 50 to 200 repeats, the region of DNA becomes unstable and is referred to as a premutation. A full mutation consists of over 200 CGG triplet repeats.

The full mutation typically causes abnormal methylation (methyl groups attach to components of the gene) of FMR1. Methylation inhibits gene transcription and thus protein production. The reduced or absent protein product (FNIRP) is responsible for the clinical features of fragile X syndrome. Approximately 15% to 20% of males with a full mutation don't have fragile X. This may be explained by either the ability of unmethylated portions (of their mutated FMR1) to be transcribed for eventual protein production, or that these males are mosaic for the FMR1 premutation. In asymptomatic mosaic males it's believed that the cells with a premutation can produce enough protein to compensate for the cells that contain a full mutation and consequently produce no protein.

Approximately 50% of females who inherit a full mutation from their mother have clinical features of fragile X syndrome. This is primarily due to the normal process of random X inactivation. At the time of meiosis, both X chromosomes must be activated. However, shortly after the zygote stage, an X chromosome is inactivated in every cell. Clinically measurable effects of the full FMR1 mutation will be more likely in relevant tissues or organs that have a disproportionate number of cells in which the normal X chromosome has been inactivated.

Males with a premutation don't have fragile X. They're considered unaffected or normal-transmitting males. Because males have only one X chromosome, all daughters of a transmitting male will inherit their father's X chromosome with the premutation. None of the male's sons will inherit the premutation because they inherit their father's Y chromosome rather than the X chromosome.

Females with the premutation don't have fragile X syndrome. However, the premutation can expand into the full mutation range (>200 CGG triplets) when it's transmitted from a premutation carrier mother to her offspring. This expansion can occur during or after maternal meiosis. Therefore, the following possibilities exist for every pregnancy of a mother with a premutation.

❑ A female conceptus receives the mother's X chromosome with the nonmutated FMR1 gene. She won't be affected with fragile X. None of her future offspring will be at risk for inheriting the syndrome from her.

❑ A male conceptus receives the mother's X with the nonmutated FMR1 gene. He won't be affected with fragile X. None of his future offspring will be at risk for inheriting the syndrome from him.

❑ A female conceptus receives the mother's X chromosome with the FMR1 premutation. She'll be a carrier like her mother but won't have fragile X syndrome. Her future offspring will be at risk for inheriting a full mutation from her.

❑ A male conceptus receives the mother's X with the FMR1 premutation. He won't be affected with fragile X. All of his future daughters but none of his future sons will inherit the premutation from him.

❑ A female conceptus receives the mother's X chromosome with the FMR1 gene whose premutation expanded into a full mutation during or after maternal meiosis. Depending on the outcome of random X inactivation, the daughter may have clinically definable fragile X syndrome. Her future offspring will be at risk for inheriting the full mutation and, thus, the syndrome from her.

❑ A male conceptus receives the mother's X chromosome with the FMR1 gene whose premutation has expanded into a full mutation during or after maternal meiosis. In 85% of cases, the son in this situation will have fragile X syndrome. Evidence indicates, however, that the FMR1 gene in the son's gametes will have the CGG triplet repeat within the premutation range, not the full mutation range like his somatic cells. Therefore, his future daughters wouldn't be expected to have fragile X syndrome.

It should be noted that most commonly the FMR1 status of a mother is subsequently determined after her son is clinically and later molecularly diagnosed with fragile X syndrome. Health care professionals need to be sensitive to the fact that the mother could either find out she's a carrier of a premutation or she has a full mutation. Consequently, not only will she learn her son's diagnosis but she, herself, could be diagnosed with fragile X if she has a full mutation and clinical symptoms.

Fragile X syndrome is estimated to occur in about 1 in 1,500 males and 1 in 2,500 females. It has been reported in almost all races and ethnic populations.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Mental retardation: Causes and incidence
(Professional Guide to Diseases (Eighth Edition))

A specific cause is identifiable in only about 25% of people who are mentally retarded, and, of these, only 10% have the potential for cure. (See Causes of mental retardation.) In the remaining 75%, predisposing factors, such as deficient prenatal or perinatal care, inadequate nutrition, poor social environment, and poor child-rearing practices, contribute significantly to mental retardation.

Prenatal screening for genetic defects (such as Tay-Sachs disease) and counseling for families at risk for specific defects have reduced the incidence of genetically transmitted mental retardation.

An estimated 1% to 3% of the population is mentally retarded, demonstrating an IQ below 70 and associated difficulty in carrying out tasks required for personal independence.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Mental Retardation: Mental Retardation - epidemiology
(The 5-Minute Pediatric Consult)

Found in both sexes and all racial and socioeconomic groups

Mental Retardation - prevalence

• Prevalence of mental retardation is generally listed as 2–3% of the population.
• Of the different subcategories of mental retardation, the mild form is the most prevalent, at 85% of those with mental retardation.
  • Profound mental retardation is least prevalent, at ~1% of this group.

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Source: The 5-Minute Pediatric Consult, 2008

About prevalence and incidence statistics:

The term 'prevalence' of Fragile-X Syndrome usually refers to the estimated population of people who are managing Fragile-X Syndrome at any given time. The term 'incidence' of Fragile-X Syndrome refers to the annual diagnosis rate, or the number of new cases of Fragile-X Syndrome diagnosed each year. Hence, these two statistics types can differ: a short-lived disease like flu can have high annual incidence but low prevalence, but a life-long disease like diabetes has a low annual incidence but high prevalence. For more information see about prevalence and incidence statistics.

Footnotes:
1. Pathophysiology of Disease, Stephen J. McPhee, Vishwanash R. Lingappa, Willim F. Ganong, Jack D. Lang, Prentice Hall, 1995