Screening for Fragile X Syndrome (Murray et al.) - NIHR Journals ...

Natural history6affected individuals experience difficulty innumeracy and visual–spacial tasks, although theyperform relatively better in language skills, particularlyreading (Freund & Reiss, 1991; Miezejeski etal, 1986). Speech is often delayed and is generallydescribed as echolalic, perseverative (i.e. repetitionof words, phrases or topics) and cluttered (Sudhalteret al, 1990; Sudhalter et al, 1992). The abilityto process information sequentially, such as followinga set of instructions given together, createsparticular challenges (Kemper et al, 1988).Behavioural featuresUnlike many of the physical features, such as thelong face or macro-orchidism, which only becomeapparent around the onset of puberty, the principalbehavioural characteristics are often already observablein early childhood. However, the heterogeneousnature of fragile X syndrome means that notevery child will display characteristic behaviouralfeatures. Social impairment may present as anxiety,sensory defensiveness, ritualistic behaviour, selfinjury(mainly hand-biting) and other stereotypedbehaviour such as hand-flapping (Hagerman et al,1986). Poor eye contact, to the point of turningthe head and torso away from the line of gaze, isalso not uncommon (Hagerman et al, 1986; Wolffet al, 1989).AutismAt one time the behavioural features were believedto be associated with autism (Brown et al, 1982;Meryash et al, 1982; Partington, 1984; Levitaset al, 1983), but the relationship between the twodisorders was not confirmed by subsequent studies(Einfeld et al, 1989; Fisch, 1992). It is now generallyaccepted that although autism does occur in maleswith the fragile X syndrome, the incidence is nogreater than in other groups of children withlearning disabilities (Einfeld et al, 1989; Einfeldet al, 1994). Detailed neuropsychological studiescomparing the two disorders have shown that maleswith fragile X syndrome more commonly display arange of autistic-like features that differ subtly fromtrue autism (Schapiro et al, 1995; Freund & Reiss,1991; Cohen et al, 1989). For example, some studieshave found that although problems of languageand communication are common to bothdisorders, males with fragile X syndrome appear tohave a greater understanding of conversation thanautistic males (Sudhulter et al, 1990; 1991).Attention-deficit disordersSeveral studies have reported on the presence ofattention deficits and hyperactivity in young boyswith fragile X syndrome (Largo & Schinzel, 1985;Fryns et al, 1984c; Finnelli et al, 1985; Hagerman,1987). This behaviour becomes apparent in thesecond year of life and may, to some extent,improve after puberty (Largo & Schinzel, 1985).Controversy exists over whether attention-deficit,hyperactivity disorders are specific to fragile Xsyndrome. It has been suggested that the behavioursimply relates to the severity of the learningdisability in general (Einfield et al, 1991). However,recent research indicates that, when compared tothose with similar learning disabilities, boys withfragile X syndrome are more restless and fidgety,and have poorer concentration (Turk, 1995b).Also, in children with fragile X syndrome who havemild learning disabilities, the presenting featuresmay be significant hyperactive and attentionalproblems (Hagerman et al, 1985).TreatmentAlthough fragile X syndrome is not curable, thereare a number of medical, educational, psychologicaland social interventions that can improvethe symptoms.Medical treatment is available for common problemssuch as recurrent ear infections, strabismusand joint laxity. Treatment of ear infections isparticularly important, since existing or potentiallanguage deficits may be further complicated byfluctuating hearing loss.Folic acid medication is sometimes used in anattempt to control the behavioural problems.Interest in the therapeutic potential of folic acidarose from the observation that fragile site expressionin vitro could be reduced by the its addition tothe culture medium. Lejeune (1982) first reportedanecdotally on the beneficial effects of folic acidfor improving ‘psychotic-like’ behaviour in affectedmales. Seven out of eight patients studied showeddramatic improvement, although the method usedto measure improvement was not specified. Therehave since been other such reports, including asurvey carried out by the Fragile X Society (unpublished)in which 10 out of 16 children treated weresaid to have improved. However, seven doubleblind,placebo-controlled crossover studies on atotal of 65 affected males have failed to demonstratea marked improvement when hyperactivebehaviour and attentional problems were measuredby standard objective instruments (see Table 1).The patients only showed an improvement whenthe assessment was judged by the impressions ofparents, doctors and teachers. It is possible that the