14 May 2008
Mrs A had two older sons at the time she became pregnant with her third child. Her oldest son was healthy. In the early stages of her pregnancy with her third child, her second son was diagnosed as having Fragile X syndrome
Fragile X (FraX or FRAXA) is a potentially seriously disabling inheritable condition causing intellectual, behavioural and physical problems.
Mrs A and her husband were clear they did not wish to have a second child with Fragile X syndrome and therefore requested pre-natal diagnosis. They had decided that if the fetus were affected by Fragile X, Mrs A would have a termination of the pregnancy. Testing for Fragile X was performed in the early stages of the pregnancy (on fetal material from a CVS – chorionic villus sample) and was reported as ‘all clear’ - Mrs A was advised that her baby did not have Fragile X syndrome, so went ahead with the pregnancy and gave birth to her third son. Mrs A, though not herself affected, was diagnosed as a carrier of the Fragile X gene.
The baby boy was delayed in reaching his milestones. Mrs A asked for re-testing but this was refused – she and her husband were told the ‘all clear’ antenatal testing was conclusive. When her third son was four, Mrs A was so concerned about him she insisted that he was genetically reviewed. The family had by then moved and were in the catchment area of a different genetic testing laboratory. The child’s DNA was re-tested and he was diagnosed as having Fragile X syndrome, like his older brother. He has substantial intellectual, behavioural and some physical disabilities because of his Fragile X syndrome.
Mrs A brought a claim in respect of the birth of her third son, and the substantial costs of meeting, for his lifetime, his special needs (resulting from Fragile X syndrome). Liability was admitted shortly after the issue of proceedings and damages of £1,800,000 (£1.8m) have just been agreed.
Mrs A’s claim was dealt with by Anne Winyard
– joint head of the Clinical Negligence department – and her team, including her then assistant, Dr Darren Conway, a former research geneticist.
What testing was used?
Only one form of DNA testing (so called PCR – ‘polymerase chain reaction’) was used to test the fetal DNA from the antenatal CVS sample. If an additional and complementary form of DNA test (called ‘Southern Blot’) had also been used to test the antenatal sample, the Fragile X would not have been missed.
PCR is a screening test, which detects normal and pre-mutation genetic sequences. A pre-mutation genetic sequence will not give rise to the syndrome in the individual who carries it, but may do so in their offspring. If PCR shows the presence of normal and/or pre-mutation genetic sequences, that is regarded as excluding the presence of a full Fragile X mutation, in a male baby.
Southern Blot on the other hand is a diagnostic test for the full Fragile X mutation – the mutation that causes Fragile X. Southern Blot testing was used to diagnose Mrs A’s carrier status.
UK testing guidelines have now been tightened up to ensure antenatal Fragile X diagnosis does not fail because only one, rather than both, tests are used.
What is Fragile X (FraX or FRAXA)?
Fragile X (FraX or FRAXA) is the most common known cause of inherited intellectual disability. Because the condition is inherited, the diagnosis of an individual with Fragile X has serious implications for other family members (who may be carriers) and their future children. Both men and women can be carriers of the condition and the condition itself affects both males and females.
In Fragile X, one of the genes (called FMR1) on the X chromosome is faulty – affecting synthesis of a protein necessary for brain development. The reason boys are usually more severely affected by Fragile X than girls is that they have only one X chromosome. Girls may have only mild disabilities because they have a second normal X chromosome, which can mask the adverse effects of the faulty one.
Apart from intellectual disability, an individual with Fragile X may be hyperactive, autistic and suffer from attention deficit disorder, emotional and behavioural problems, social anxiety, gaze avoidance, mood swings and language disorder. Self-injury in the form of biting and repetitive behaviour such as hand-flapping and an insistence upon routine with a dislike of change are common. Physical features are variable but can include a large head with a long face and large jaw, large or poorly folded ears, flat feet and hyperextensible joints. About a quarter or a third of people with Fragile X are affected by epilepsy.
Information was correct at time of publishing. See terms and conditions for further details.