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5. SELECTED GENETIC DISORDERS Only approgimately 15% of causes of intellectual disabilities are known. Among those causes we know are several hundred genetic disorders. The most known is Down Syndrome. Information about Down Syndrome can be easily found elsewhere, therefore we introduce two less know conditions in this chapter. The first one is Williams Syndrome. William Syndrome is a genetic disorder, which is rare and affects around 1 person in 20 000. The reason is deletion of 7. chromosome (in area 7q11.23). This causes medical problems, including cardiovascular disease, developmental delays, and learning disabilities. These occur side by side with striking verbal abilities, highly social personalities and an affinity for music. The test which helps you find out, if your child has this syndrome is a method called FISH (florescent in situ hybridization). This test is made by blood and it´s crucial to diagnose this disease. The most common reason to make this test is cardiovascular problems – especially narrowing of an aorta, which occurs to almost every person with Williams Syndrome. The most common symptoms are: Characteristic facial appearance - wide forehead, short palpebral fissures, stellate iris pattern, low nasal bridge, bulging cheeks, large mouth, full lips. Congenital heart disease - most commonly supravalvular aortic stenosis (i.e., narrowing of one of the major blood vessels departing from the heart) Delayed psychomotor development - at an early age children take longer to learn to walk and talk. At a later age it shows varying degrees of mental disability - moving mostly in the range of mild to moderate mental retardation. Compared with other skills children very well and especially love to talk. Communication skills outweigh understanding. As a result, often causing more advanced than they actually are. On the other hand they tend to have problems processing visual-spatial information. They are often present with attention deficit hyperactivity disorder. Many children are unusually musical. The behavior of these children is very social and outgoing. They lack, however, social inhibitions and a healthy dose of wariness towards strangers.
In the Czech Republic there is just one organization which associates people with Williams’s syndrome (WS people) and their families or any other person who is in some way related to this issue. The organization is called “Willík” and was formed in 2006. In these days Willík associates or cooperates with around 30 families. The oldest member who has Williams’s syndrome is currently 25 year old girl.
The second genetic disorder we introduce is Fragile X syndrome (FXS).
Fragile X syndrome (FXS), also called Escalantes syndrome or Martin- Bell syndrome (in 1943 Martin and Bell were the first ones, who had described this condition) is genetic syndrome which is connected with physical, cognitive, emotional and behavioral problems, in some cases, the expressions of this condition are nearly imperceptible, but sometimes it has very grave consequences.
Causes As mentione above FXS is genetic syndrome, in other words it means that it is caused by change or mutation of X gene. Every human has 46 chromosomes; two of them are sex chromosomes (X and Y). Female has two X, male X and Y. And they are inherited from generation to generation. Every gene has its own name and the one causeing FXS is called FMR1. This gene cannot produce very important protein called FRMP and that is the main cause of FXS. Actually it is not so easy with this gene – it could have three forms. First one is normal gene, than it is unstable mutation which is kind of sleeping in its owner, but it could expand in future generations, the third one is full mutation, which causes fragile x, with all its symptoms.
Transmission The fathers, who are carriers of this gene, cannot pass this gene to their sons (because they are passing their Y chromosome to them) and if they pass it to their daughter it usually does not expand to full mutation. Mothers with FRM1 often pass larger version mutations to their children. If mother have one mutated gene there is 50% chance (she has two same sex genes) that their children will suffer by this syndrome. Sons, who receive this gene, are always at high risk of intellectual disability. Daughters have a bigger chance to have normal level of intelligence, but they could be intellectually disabled too (usually less than boys). Interesting paradox is that the transmission of FMR1 gene quite often increases with each passing generation. This unusual paradox is called Sherman paradox. Every 250th women and 800th men are carriers of this gene and every 5000th woman and 3600th men develop this impairment.
Diagnosis The FXS is very diverse with many various symptoms. Not everyone with FXS has the same symptoms and signs, even siblings could have another symptoms. From the medical poin of view Fragile X is proved by two kinds of molecular DNA tests – The polymerase chain reaction (PCR) and Southern Blot analysis. But FXS is also reflected in everyday life – the signs and symptoms could be divided into six categories:
Signs and symptoms Physical The most common characteristics are prolonged face with prominent chin, large ears, flat feet, low muscle tone, skeletal problems, mitral valve prolapse and macroorchidism (larger testes; males) Sensory There are many problems and disabilities of sense organs, such as ear infections, strabismus, amblyopia, refractive errors etc. People with Fragile X are often characterized by hypersensitivity to visual, auditory, olfactory and tactile stimuli. They may have problems with sharp illumination (summer sun), loud noises (classes, crowds), with touching and they can find material textures which could be irritating for them. Intelligence and learning People with wrong FMR1 gene have deficits in cognitive and intellectual functions. The mutation of X gene causes mental retardation. This leads to problems in learning and adaptation. Latest research found out the fields which are affected the most – it is memory (especially working memory), executive and cognitive functions and speed of processing the information. This all things are closely connected with IQ – children with FXS have 2.2 times slower learning rate than children who are not affected by FXS. Speech and language The main manifestation which is most noticeable is the paraverbal speech. It sounds nervous, cluttered and with bad intonation.
Social and emotional The most typical for FXS is social anxiety. It means that these people are shy, they have aversion to eye contact. The time before they begin the interaction is very long. Their anxiety is largely due to memory problems – especially the face encoding. It was found that people with Fragile X have decreased activation in the prefrontal regions of the brain which are associated with social cognition – in practice it means that they could not encode, preserve and recall the faces of people, whom they are even in closest contact
Behavioral Most typical sign in behavior is social anxiety, atypical social development, stereotypic movements and perseverations problems with social cognition. Children are often hyperactive with hypersensitivity to sensory stimulations. Males (who have usually severe kind of FXS than females) tend to have increased occurrence of OCD (obsessive-compulsive disorder), depressions, phobic anxiety, somatization, depression and they are more prone to Fragile X- associated tremor/ataxia syndrome (FXTAS). Females have often mood disorders, avoidant behavior and depression than non affected women. |