PHG Foundation | Timing of screening for Fragile X Syndrome

Timing of screening for Fragile X Syndrome
29 July 2010 | By Dr Philippa Brice | Research article

Fragile X syndrome is the most common inherited form of learning disability. Caused by expansion of a section of the X-chromosome, it affects around one in 3,600 men (see BBC Health); women are less frequently affected and may have milder symptoms. Pre-mutation carriers with smaller expansion regions may not show symptoms but can develop related health problems later in life and may have children affected by Fragile X.

Population screening for Fragile X has been considered in different countries for some years now (see previous news), but raises distinct issues compared with other inherited disorders, due to the variable risks to pre-mutation carriers and female mutation carriers; the latter show very variable clinical features ranging from unaffected to severe learning disability.

A newsystematic review has examined published evidence relating to population-based screening for fragile X in women of reproductive age (ten studies) and newborn babies (one study) between 1991 and 2009 [Hill MK et al. (2010) Genet Med. 2010 Jul;12(7):396-410]. This review included analysis of papers examining psychosocial elements of screening: two forming part of the screening studies, and nine additional articles.

The authors found a general lack of evidence; although published research showed population screening to be largely effective, all the studies were observational, as opposed to controlled (comparing screening with alternative screening or no screening). Uptake of testing was found to range from 7.9% to 92% in different prenatal screening studies, 79% for the newborn study. Women premutation carriers identified by screening largely took up the offer of fetal testing, with a variable proportion opting to terminate affected pregnancies.

The challenges of providing effective genetic counselling to affected women and families who knew little or nothing about fragile X syndrome were noted; although he condition is common, it is not well recognised in the general population in the way that some other genetic disorders such as cystic fibrosis are. The main conclusions were that controlled studies should be conducted to examine both the technical and psychosocial elements of screening for Fragile X, and that specialised guidance for genetic counselling would be required.

Newborn screening was found to have more limitations than adult carrier screening. As reiterated in an accompanying commentary, although prompt identification of full mutation carriers can allow improved care, it cannot predict which female carriers will show clinical symptoms, and also identifies premutation carriers at risk of adult-onset conditions and other forms of X-chromosomal abnormality [Coffee B. Genet Med. 2010 Jul;12(7):411-2 ].

In addition to improved education and counselling, the timing of screening would appear to be crucial, with preconception screening preferable to prenatal screening among adult women, and the suggestion that optional infant screening would be a better option than newborn screening
PHG Foundation | Timing of screening for Fragile X Syndrome