Fragile X Syndrome

Fragile X Syndrome is a genetic hereditary disorder characterized by autistic-type behaviors, moderate to severe mental retardation, hyperactivity and behavioral problems. In fact, it is considered the second most common cause of mental retardation in boys after Down syndrome.

Dysmorphic features are often observed, such as a long face with protruding ears and large testis in puberty.

Globally, it is estimated that the frequency of the syndrome is 1: 3600-1: 4000 boys and 1: 4000-1: 6000 girls.


Males affected by the syndrome are characterized by moderate to severe mental retardation. Females can also be affected, but generally with mild mental retardation. Behavioral problems and lingering delay are common features of Fragile X Syndrome. About 15% to 20% of people with Fragile X Syndrome develop autistic type behaviors.

Special characteristics

People with Fragile X Syndrome also have several identifiable physical features:

  • High palate arch.
  • Strabismus (lazy / lazy eye).
  • Big ears and a long face.
  • Large testicles in males.fragile-X-syndrome
  • Mild muscle tone.
  • Flatfeet.
  • Mild heart valve abnormalities (less often).

Typical autistic behaviors in Fragile X

  • Poor eye contact.
  • Fingering of the hand.
  • Strange gestures.
  • Hand bending.
  • Poor sensory skills

How is Fragile X syndrome inherited?

Fragile X syndrome is considered a viable residual disease because the responsible area for the onset of the syndrome is on chromosome X.

However, it does not follow the rules of Mendelian heredity because  boys with the mutation have been referred who are not sick, but also girls with severe mental retardation.

The disease is caused by the extension of the CGG polymorphic trinucleotide sequence and the hypermethylation of CpG islet to the region of the FMR-1 gene promoter.

There are several scales that affect the clinical picture of an individual and the occurrence of the disease and are directly proportional to the number of repeats of the CGG sequence:

  • Normal: 6-44 copies, with more frequent 29 or 30 copies
  • Intermediate: 45-54 copies
  • Premutation: 55-200 copies characterizing the carriers and may develop into a complete mutation when transferred by females.
  • Complete Mutation: >200 repeats – is detected in patients and causes hypermethylation and translational deactivation of the FMR-1 gene, resulting in non-production of the FMRP protein.

Since a woman has two X chromosomes, in the case of premutation or full mutation there is a 50% chance of transmitting the X chromosome with the mutation in each pregnancy and a 50% chance of transmitting the normal X.

Because males have only one X chromosome, the fathers carrying the mutation will pass it on to all their daughters and none of their sons (they will pass their Y chromosome to their sons). When a father passes the premutation to his daughters, it usually does not extend to a complete mutation. This seems to only happen when the mother’s premutation passes on the next generation.

The probability of increasing CGG repetitions in the next generation is related to the magnitude of premutation. The greater the number of CGG repeats of the mother, the greater the chance of extending to full mutation if transmitted.

The syndrome is diagnosed by molecular screening based on the PCR reaction to detect the number of repeats of the CGG trinucleotide of the FMR-1 gene.



Various treatments are recommended for people with this disorder, including mild medications for behavioral problems and  therapy for speech and language, and improvement of sensory functions. Families are also encouraged to seek genetic counseling to understand the inherited nature of the syndrome and to discuss among the family members the possibility of other people or future offspring or other individuals who may be affected by this disorder.

Premature Ovarian Insufficiency and Fragile X syndrome



Premature Ovarian Insufficiency (POI) is the condition in which the ovaries, which produce and release an egg each month, stop working before the woman reaches the age of 40 and is characterized by circulatory disorders, low estrogen levels combined with high levels of gonadotrophins. When the ovaries stop working, women are no longer ovulating and are infertile or sterile.

What Causes POI According to the American College of Obstetricians & Gynecologists (ACOG)?Genetic disorders: Turner syndrome (chromosomal abnormality) and Fragile X syndrome.


  • Damage of the ovaries from toxic substances (chemotherapy) or from radiation (radiotherapy).
  • Multiple endocrine disorders (eg hypoparathyroidism and hypotalism).
  • In 4% of cases there is evidence that it is an autoimmune disease
  • Less often, it is the result of invasive or infectious diseases (eg mumps) and even operations in the pelvic region.
  • Most of the time the cause is unknown, can not be found.
  • Many times there is a family history. Women with a family history are more likely to have POI.

Detection of Fragile X is recommended for women with early menopause, and for men who show Fragile X / termor Syndrome that occurs after the age of 50-60 years

Premutation carriers do not develop the full neurological image of the full mutation carriers, but suffer from POI and may experience Fragile X tremor-ataxia syndrome or behavioral disorders.

Approximately one third of premutation patients have poi and it is considered that the number of CGG repeats affects the onset of cessation of ovarian function. The rest of the premutation carriers, although maintaining a normal menstrual cycle, have signs of ovarian aging, as evidenced by the duration of the follicular phase of the cycle and the levels of oestradiol, progesterone and gonadotropins.

Frequency of POF


It is estimated that one woman in 250 under the age of 30 and one in 100 under the age of 40 has premature menopause, which is due to early ovarian failure, in which follicles deplete or under-operate, even from puberty.

According to a CDC study in 2012, the frequency of Fragile X premutation is as follows:

  • 1 in 151 women
  • 1 in 468 men

These data are important because both men and women are at risk of having symptoms associated with Fragile X-related disorders.

  • Women with premutation reported their last menstrual cycle at an earlier age than women without premutation (48 vs. 51 years).
  • Men and women with premutation were more than four times more likely to report dizziness or fainting than those without premutation (18% versus 4%).
  • Men and women with premutation were more than twice as likely to report numbness as opposed to those without premutation (29% versus 13%).


Allingham-Hawkins, D. J., Babul-Hirji, R., Chitayat, D., Holden, J. J. A., Yang, K. T., Lee, C., Hudson, R., Gorwill, H., Nolin, S. L., Glicksman, A., Jenkins, E. C., Brown, W. T., and 27 others. Fragile X premutation is a significant risk factor for premature ovarian failure: the international collaborative POF in fragile X study–preliminary data. Am. J. Med. Genet. 83: 322-325, 1999.