Fragile X syndrome: symptoms, causes and support

Fragile X syndrome (FXS) is a genetic condition that can cause a wide range of difficulties with learning, language, attention, emotions and behaviour. The Fragile X Society says it affects around 1 in 4000 males and 1 in 6000 females. Mencap notes that it affects both boys and girls, though boys are often more severely affected.

The Society also describes fragile X as a family of conditions. As well as the syndrome itself, people who carry a smaller change, called a premutation, can develop related conditions in adulthood.

No two people are the same. Some individuals have only a few of the characteristics described below.

The Fragile X Society says learning disability occurs in almost all males with fragile X, to differing degrees. A severe disability is rare. Because females have two X chromosomes and usually only one is affected, the impact varies: some appear unaffected, others have mild learning disability and some more severe.

Speech and language are usually delayed with continuing communication problems. Mencap says someone with fragile X might have a short attention span, be easily distracted, act impulsively, feel restless or very active, and have heightened senses.

Some people show autistic-like features, including avoiding eye contact, anxiety in social situations, a strong preference for familiar routines, and hand flapping or hand biting. The Society says up to 50% of males and around 15% of females may receive a dual diagnosis of autism. NHS GeNotes gives a higher range of 50% to 70% for autism spectrum disorder, so published figures differ.

• Strengths named by the Fragile X Society include good imitation skills, visual learning, long-term memory, likeable personalities, sensitivity to others' emotions and a good sense of humour.

• Some people develop epilepsy, according to the Society and Mencap.

• Connective tissue features can include low muscle tone, flexible joints, flat feet, recurrent ear infections and mitral valve prolapse.

• Physical features can include a long, narrow face with prominent jaw and ears, but these are rarely obvious in young children, which is one reason diagnosis can be delayed.

• NHS GeNotes also lists enlarged testes after puberty in affected males.

GeNotes explains that fragile X syndrome is a triplet-repeat expansion disorder. A short DNA sequence called CGG is repeated within the FMR1 gene on the X chromosome. When it expands beyond 200 repeats, called the full mutation, the gene is silenced and the FMR1 protein is lacking.

Repeat numbers fall into bands. People with 55 to 200 repeats are premutation carriers, who do not have fragile X syndrome and may be entirely well. GeNotes says certain conditions are linked to carrier status.

The Fragile X Society estimates about 1 in 250 females and 1 in 600 males carry the premutation. Carriers may develop fragile X premutation associated conditions such as FXTAS and FXPOI.

GeNotes says that around 40% to 75% of male and 16% to 20% of female premutation carriers develop fragile X tremor-ataxia syndrome (FXTAS) later in life. Around 25% of female carriers experience fragile X-associated primary ovarian insufficiency (FXPOI), which can lead to reduced fertility and early menopause.

Because of this, a diagnosis in a child can raise questions for other relatives, who may want genetic counselling.

GeNotes says the condition is X-linked. An affected female has a 50% chance of passing it to any child. An affected male passes it to all his daughters and none of his sons.

A premutation can expand to a full mutation when passed on by a mother, depending on its size. Expansion does not usually happen when a father passes on the gene. Genetic counselling through clinical genetics services helps families understand the risks and options.

Mencap says fragile X can be diagnosed with a blood test and cannot be diagnosed from physical features or behaviour. Prenatal diagnosis is possible, and carriers can also be identified.

GeNotes says that fragile X can now be reliably diagnosed through whole genome sequencing. If it is suspected, testing is usually through broader genetic tests that also look at other causes of syndromic intellectual disability.

Families often seek an assessment when a child is late to talk, has difficulty with attention or social interaction, or when a relative has been diagnosed. A GP can refer to a paediatrician or clinical genetics service.

There is no cure. GeNotes says management of children is complex and should be delivered by a multidisciplinary team. Mencap says most people need support with speech and language and with social and emotional interaction, and that the right support enables a fulfilling life.

Support is usually planned around the person. It may involve speech and language therapy, education plans, occupational therapy, behavioural and mental health support, and treatment of epilepsy if it develops. The Fragile X Society offers information, resources, family weekends and a conference for families and professionals.

We could not find detailed UK clinical guidance on specific medicines in the sources used for this page, so treatment decisions should be made with the specialist team.

Speak to a GP or health visitor if a child has delayed speech or development, or if someone in the family has been diagnosed with fragile X. Seek help from the GP for new difficulties with balance, tremor, memory or periods in an adult with a known premutation.

A first seizure, a seizure lasting longer than usual, or a person who does not recover normally afterwards needs emergency help. Call 999. Use NHS 111 when you need advice but it is not an emergency.

Most families start with a GP, health visitor or nursery concern, followed by paediatric and genetics assessment on the NHS. Education, health and care planning runs alongside through the local authority and school.

A private paediatric or neurodevelopmental assessment may shorten waiting, but genetic diagnosis, family testing and long-term support are usually organised with NHS genetics and community teams, and records should be shared between providers.