Psychiatric and Autistic Comorbidity in Fragile X Syndrome Across Ages

Abstract

Fragile X syndrome is caused by CGG trinucleotide repeat expansion within the fragile X mental retardation 1 gene, when repeat number exceeds 200. The typical psychiatric profile of fragile X syndrome patients includes cognitive and behavioral deficits, psychiatric comorbidity, and autistic characteristics. Specific psychiatric features have not yet been clarified, specifically in relationship to age and genetic characteristics. The objective of this study was to characterize psychiatric comorbidities in subjects with fragile X syndrome at different ages. Subjects with fragile X syndrome and their unaffected siblings were recruited and their parents filled out functional-behavioral and psychiatric comorbidities questionnaires. Adolescents with fragile X syndrome showed decreased prevalence of functional-behavioral deficits. Incidence and severity of most psychiatric comorbidities were lower in older subjects. Incidence of generalized anxiety disorder increased with age in the fragile X syndrome group. The typical profile of patients with fragile X syndrome changes with age. Unaffected siblings exhibit anxiety and motor tics.

Fragile X Syndrome: A Review of Associated Medical Problems

“…Tics were reported in 16% of 152 people with FXS in a cohort from the United States, 52 and 36% and 45% of patients were reported to have motor and vocal tics, respectively, in a cohort of 22 patients with FXS from Israel. 53 The high frequency reported in the latter study may reflect confusion between stereotypies and tics in parent reports, which can be challenging to distinguish without history and neurologic examination data. The FXCRC database suggests that motor tics are uncommon in FXS, occurring in about 6% of affected people; this rate is not notably different from reports of combined motor and vocal tic frequency in the general population, 54 so no special management is indicated with respect to tics in FXS.…”

Effects of clonidine and methylphenidate on motor activity in Fmr1 knockout mice

“…Tranfaglia [40] reported that the presence of ADHD in those with FXS does not appear to follow a linear trajectory-young children may present as hypoactive, with hyperactivity increasing dramatically during the preschool years only to decline as children reach adolescence. Preliminary data suggest that the incidence of ADHD may be lower for adolescents than children and that different patterns of inattention and hyperactivity between those under and over 18 exist [43]. This developmental change might suggest which medications may be more effective and when.…”

Fragile X syndrome – a common disease rarely diagnosed

“…Hence, my observed frequency is in agreement with data from publications (5% to 60%). Cooccurrence of FXS and ASD is an additional risk factor in regard to central nervous system anomalies [6,9].…”

“…Typically, the psychiatric profile involves behavioral and cognitive symptoms, and includes hyperactivity, attention problems, anxiety, mood liability, aggression, self-injury, poor eye contact, self-talk, hand flapping, hand biting, as well as perseverative language [2,4,5]. Affected males with FXS are also at increased risk of experiencing liferelated psychiatric problems such as anxiety, depression and loneliness [6]. In my study, the presence of autism spectrum disorder was an important marker of independency.…”