Dr. Josep Artigas
Hospital Parc Taulí, Sabadell

Fragile X Syndrome (FXS) is a disease in which the most important clinical signs come from a dysplasia in the connective tissue, hormone dysfunction, and the microstructural alterations in the nervous system.

The neurological signs are very important in Fragile X Syndrome, as they define behavior, the cognitive distortions, and possible association with epilepsy.


The first signs of FXS are hipotonia and the delay of basic development. Early manifestations of these traits prompt the first suspicion of FXS at around two years of age, or sometimes before. In our society, average diagnosis happens at 3 years, which can be considered as early diagnosis.

During the first year, the muscular tone is low, and can be obseved in routine examination. This can be expressed as poor head holding capacity and laxed limbs that can lead to misinterpretation as the delay in language acquisition and motor development only appear at a later stage. 

A study based on a opinion poll with 106 patients revealed that the average age for starting to walk was 19,2 months, and the average for the first words was 2,8 years. In girls the average was lower: starting to walk at 14,8 months, language at 1,8 years. These results explain why medical attention is normally sought only after language or motor development delay is observed.


The FXS presents different behaviour features that are typical of the so called behavioural phenotype; this depends on a series of hormone and neurological alterations which take place specifically in FXS.

Almost 20% of FXS individuals show autistic disorder, while just 2 or 3% of autistic people are FXS. There are possibly important keys to reveal the misteries of autistic disorders hidden in FXS. However, this association is not bizarre as the brain areas where we find FXS disorders overlap those related to autism. These parts of the nervous system involve the cerebellum, the thallum and the caudate.

The most outstanding results in behavior according to the opinion poll are expressed in figure 1.

The factors that influence this standard behavior are:

  1.  Sensory integration problems
  2. Anxiety
  3. Executive dysfunction
  4. Attention disorder
  5. Language disorder

These factors generally explain the behaviour of children with FXS. The knowledge on the basic causes of behavior can also provide future therapeutic possibilities.


Cognitive aspects can not be dissociated from behavioral aspects, as the behavior affects the capacity and intellectual skills of patients with SXF.

In general, a FXS individual’s IQ is low. However, this data must be interpreted according to differing circumstances. The attention deficit and the high levels of anxiety may mask real IQ values. Even outside an experimental setting, it may be that a FXS individual blocks the full display of social skills. The IQ is an average measure of diverse skills, and while some of them are enhanced, others lie  within normal range.

After these explanatory notes, studies conducted to measure the intellectual abilities of children with SXF, showed the following results:


– Male full mutation: 41

– Men with mosaic: 60

– Men with partially methylated full mutation: 88

In general, part of the variation in FXS IQ can be explained by the amount of FRMP protein produced.


In Fragile X Syndrome, bioelectrical activity alterations of the brain can generate seizures. This occurs in 14% of patients.

The average age for the first crisis is 5,4 years (+ / – 2,1). The median age at which convulsions stop is 7,7 years (+ / – 2,8). The crises include generalized, partial complex and partial simple seizures

Crises involve generalized convulsive movements of the four limbs, accompanied by loss of consciousness. They last a few minutes and are followed by a post-critical state of relaxation and sleep. During the crisis there may be a discreet presence of foam in the mouth. Release of urine can also happen. On awakening, the child may experience a slight feeling of discomfort or headache. Such crises, although they are very alarming, do not involve any serious risk. Do not think that this type of crisis causes brain injury or that the child can die from it.

The simple partial seizures occur when convulsions start in one part of the body. They can be generalized and in this case they are called secondary generalized partial seizures. The partial seizures may also be a symptom of sensory isolation. Although these are much less frequent, they are more difficult to identify because they can be experienced as a visual or auditory sensation which is hard to describe.

Complex partial seizures involve consciousness alterations in situations of partial disconnection from the environment. The child can maintain some contact during the crisis, but expresses a state of bewilderment, indifference or absence. They can pronounce strange words and inconsistent behavior. They can also be accompanied by automatic movements with the lips, tongue or hands. If it is prolonged, it can be followed by loss of consciousness.

Sometimes seizures are febrile. In these cases the risk of developing crisis without a fever is also greater than febrile seizures in children unaffected by FXS. There may also be an epileptic state, in other words, a seizure that lasts more than half an hour. It is not surprising that seizures appear during sleep.

The performance of relatives during the convulsive episode should be calm. Clothing must be set loose and the child’s head turned to one side. We must not place anything in his mouth. Any nearby object which may cause damage must be removed. Once the crisis has stopped, we must let him sleep if that’s what he wants. If the crisis lasts for more than 5 minutes, we should go to an emergency center where Valium will be administered rectally, especially when the crisis persists. In some cases the neuro-pediatritian may prescribe Valium rectally to be administered by the family in case of repeated seizures at home. The rectal valium is prepared in the form of an enema. In crises lasting more than 2 or 3 minutes, the dose prescribed should be administered rectally, slowly during a couple of minutes, pressing the buttocks of the child after the administration so that the drug cannot be discharged.

A few days after the crisis an electroencephalogram (EEG), may be performed for the doctor to acquire useful information. In case of repeated crisis, preventive drugs may be prescribed. The evolution of epileptic seizures, can be easyly controlled, and usually disappear and the anticonvulsionant medication can be withdrawn after a period set by the neurologist in each case.


Fragile X Syndrome diagnosis suspicion is prompted by clinical signs and confirmation is always dependent on the genetic study. However, other tests are performed such as EEG. The EEG provides useful information on epilepsy and possible Fragile X expression. It may also be useful to explore aspects of behavior, although these are not yet fully clear.

Brain magnetic resonance imaging (MRI) or cranial computed tomography (CT) are also commonly requested. Neither test provides diagnostic or prognostic information, so they must not be considered as routine tests.

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