Fragile X is the most common identifiable form of inherited intellectual disability (see entry, learning disability). It has a prevalence of about 1 in 4,000 males and 1 in 8,000 females. The cause is an abnormal expansion of DNA just above the tip of the X chromosome's long arm, which may be passed from one generation to the next.

Intellectual disability varies from mild to severe. Girls and women who have a fragile X chromosome are often of normal intelligence. However up to a third have learning problems which are usually mild or moderate but can occasionally be severe.

Other problems experienced by affected individuals include delayed and distorted speech and language development. There can be difficulties with the social use of language, with continuing speech anomalies, repetitive behaviour, attention deficits and overactivity, and autistic-like features, such as poor eye contact, hand flapping, social anxiety, abnormal shyness and an insistence on routine.

Physical features ascribed to fragile X syndrome include a relatively large head, a long face with prominent ears, largish jaw and double-jointedness. However these are rarely obvious in affected individuals. Ten to thirty per cent of people with fragile X syndrome develop epilepsy.

Diagnosis is by blood test usually for the change in the gene using DNA analysis.

Inheritance patterns
A carrier woman has a fifty per cent chance of passing on the fragile X chromosome to her children. Of these, males are likely to be affected by the syndrome, whilst daughters have a 1 in 3 chance of being clinically affected.

Men can also be unaffected carriers of the fragile X chromosome. In such cases the genetic change is passed to all daughters, but to none of the sons. These daughters will themselves be unaffected but at risk of having affected children. Any sons of carrier males will be completely unaffected as they do not receive their X chromosome from their father.

Prenatal diagnosis
Prenatal diagnosis is possible by chorionic villus sampling or fetal blood sampling. This is likely to give a definitive answer for affected males but cannot always distinguish affected from unaffected carrier females.

Psychological and behavioural characteristics
Intellectual disability is common in people who carry the Fragile X gene, although abilities do span a wide range. Approximately eighty per cent of males have learning disabilities. These are mostly in the mild to moderate range, but about one-third have severe learning difficulties. Overall, verbal abilities tend to be better than performance abilities, with relative strengths in vocabulary, aspects of simultaneous information processing, and some visual perceptual tasks. Affected individuals are much weaker on tasks of abstract reasoning, sequential processing, visual-spatial abilities and short term memory and numeracy. They tend to have greater difficulty in processing new information than in learning school-related, verbally-based factual material. Even individuals with intelligence in the average or above-average range, females as well as males, show many of these features. There can be accompanying problems with shyness and social anxiety, concentration and freedom from distractibility, difficulties in organising ones thoughts and planning ahead, and maintaining direct eye contact with others. The rate of intellectual development appears to decline with age as individuals approach adolescence. The most notable decline is in the early pubertal years. This is largely attributable to difficulties in processing complex sequences of incoming information.

Language difficulties range from a complete absence of speech through to mild communication problems. Individuals often have characteristic rapid and dysrhythmic speech ('cluttering'). The rate of talking may be fast and fluctuating, with up and down swings of pitch and occasionally garbled and disorganised speech with corrections, frequent shifts of conversation from topic to topic and tangential comments. Speech may not be very fluent. Affected individuals tend to use many incomplete sentences, to repeat themselves when talking and to echo what others say to them. Articulation problems are also common.

Clumsiness and fine motor co-ordination problems occur. However, early motor development is often unremarkable. Oversensitivities to certain sights, sounds, smells, tastes and textures are also frequently witnessed.

Boys with fragile X tend to be overactive and impulsive with marked concentration problems, restlessness, fidgetiness and distractibility. Irritability, tantrums and aggressive outbursts are precipitated by environmental over stimulation, confusing situations or heightened anxiety.

Medication, in particular stimulants such as methylphenidate and dexamphetamine, have been found to be helpful for the attentional deficits in some instances. Overactivity in fragile X syndrome tends to decrease with age, but attention difficulties, restlessness and impulsivity can remain problematic for many adolescents and adults.

Autistic-like behaviours have been reported in individuals who have fragile X syndrome. These include avoidance of eye contact, stereotyped repetitive behaviours such as hand flapping, repetitive speech, resistance to environmental change, and strong preoccupations or fascinations. Only a minority of individuals have 'typical' autism. Most are affectionate and have an interest in relating socially, but have notable difficulties in social interactions and tend to be shy and anxious in social situations. Also, while affected individuals do repeat their own and other people's speech, these repetitions are believed to serve an important communicatory function, since they maintain participation in conversation while the individual is trying to process what is being said. Affected individuals are easily overwhelmed by a variety of sensory stimuli, which they find difficult to cope with. Their poor eye contact and gaze avoidance may therefore be attempts to avoid excessive stimulation. Other features such as hand-biting and hand-flapping are common, and may be provoked by anxiety, excitement and/or frustration. In many instances these features become less evident in adulthood.

Adults with fragile X syndrome often show strengths in domestic daily living skills, relative to their communication and socialisation abilities. Nevertheless, many need a degree of supported living.

Up to one-third of females with fragile X syndrome demonstrate learning and behavioural difficulties that are similar to, but usually less severe than, those seen in affected males. Some twenty-five per cent of females have learning disabilities. However, more subtle problems with learning, behavioural and emotional difficulties are common even in carrier females with a normal IQ. As is the case for affected males, verbal abilities tend to be better than performance skills, and special needs in arithmetic, visuo-spatial abilities and visual and auditory memory are common. The spoken language of carrier females may be high pitched, with repetitions and poor topic maintenance. Difficulties with planning and organising information, sustaining effort, generating problem-solving strategies, and monitoring their own performance are also apparent in many cases, as are difficulties with abstract concepts, information processing, perseverative thinking, attention (with or without overactivity) and impulsivity. Their speech is characterised by the use of tangential language and frequent changes of topic. Extreme shyness, anxiety, social avoidance, withdrawal and poor eye contact are also commonly reported in females with fragile X.

All the above features can be helped substantially by a carefully planned and instituted combination of medical, psychological, educational and social interventions tailored to the individual's particular profile of developmental and behavioural strengths and needs.

Medical text and Psychological and behavioural characteristics text written June 1997 by Dr A Barnicoat, Consultant in Clinical Genetics, Institute of Child Health, London, UK and Professor J Turk. Last updated December 2005 by Professor J Turk, Professor of Developmental Psychiatry and Consultant Child & Adolescent Psychiatrist, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, UK.

Further Online Resources
Medical texts in The Contact a Family Directory are designed to give a short, clear description of specific conditions and rare disorders. More extensive information on this condition can be found on a range of reliable, validated web sites and links to them are included in the CD-ROM version of this Directory. Further information on these resources can be found in our Medical Information on the Internet article.

FRAGILE X SOCIETY

Fragile X Society
Rood End House
6 Stortford Road
Dunmow
CM6 1DA
Tel: 01371 875100
e-mail: info@fragilex.org.uk
Web: http://www.fragilex.org.uk

The Society is a National Registered Charity No. 1003981, established in 1990. It offers support, information and advice to affected families and professionals. Family members have the opportunity to participate in research studies and the four family conferences held annually in the UK. It publishes a newsletter three times a year, has a video, helplines on education, epilepsy and benefits and has a wide range of information available, details on request. The Society has over 1,500 members.

Group details last confirmed January 2007.