Characterization, treatment patterns, and patient-related outcomes of patients with Fragile X syndrome in Germany: final results of the observational EXPLAIN-FXS study

Abstract

BackgroundAs data on the phenotype, characteristics and management of patients with Fragile X Syndrome (FXS) are limited, we aimed to collect such data in Germany in experienced centres involved in the treatment of such patients.MethodsEXPLAIN-FXS is a prospective observational (non-interventional) study (registry) performed between April 2013 and January 2016 at 18 sites in Germany. Requirements for patient participation included confirmed diagnosis of FXS by genetic testing (>200 CGG repeats) and written informed consent. Patients were followed for up to 2 years.ResultsSeventy-five patients (84.0 % males, mean age 16.7 ± 14.5 years, ranging from 2 - 82 years) were analysed. The mean 6-item score, determined according to Giangreco (J Pediatr 129:611-614, 1996), was 6.9 ± 2.5 points. At least one neurological finding each was noted in 53 patients (69.7 %). Specifically, ataxia was noted in 5 patients (6.6 %), lack of fine motor skills in 40 patients, (52.6 %), muscle tonus disorder in 4 patients (5.3 %), and other neurological disorders in 39 patients (51.3 %). Spasticity was not noted in any patient.Seizures were reported in 6 patients (8.1 %), anxiety disorders in 22 patients (30.1 %), depression in 7 patients (9.6 %), ADHD/ADD in 36 patients (49.3 %), impairment of social behavior in 39 patients (53.4 %), and other comorbidities in 23 patients (31.5 %). The mean Aberrant Behaviour Checklist Community Edition (ABC-C) score on behavioral symptoms, obtained in 71 patients at first documentation, was 48.4 ± 27.8 (median 45.0, range 5-115). The mean visual analogue scale (VAS) score, obtained in 59 patients at first documentation, was 84.9 ± 14.6 points (median 90; range 50 – 100).ConclusionsThis report describes the largest cohort of patients with FXS in Europe. The reported observations indicate a substantial burden of disease for patients and their caregivers. Based on these observations, an early expert psychiatric diagnosis is recommended for suspected FXS patients. Further recommendations include multimodal and multi-professional management that is tailored to the individual patient’s needs.Trial registrationThe ClinTrials.gov identifier is NCT01711606. Registered on 18 October 2012.

Impact of Fragile X Syndrome on Their Families

“…In fact, once behavioral and emotional problems were covaried, our results showed that families with FXS experienced a greater negative impact on feelings about parenting, finances, siblings, and the degree of difficulty of living with a child or adolescent with FXS. In general, our results are similar to those of other studies (Haessler et al, 2016;Johnston et al, 2003;Lewis et al, 2006;Raspa et al 2016).…”

“…results are consistent with previous literature (Bailey, 2012;Cordeiro et al, 2011;Haessler, 2016;Newman et al, 2015;Roberts et al, 2014). In general, a defined pattern of problem behaviors, including hyperactivity, inattention, autistic features, and aggression, along with comorbid anxiety, has emerged for this population, and this pattern is estimated to occur in up to 86% of males with FXS (Low Kapalu & Garstein, 2016).…”

“…First, parents of children with FXS in our study showed more negative feelings about parenting than parents in the control group. Haessler et al (2016) found that in a group of 64 patients with FXS, 39.1% of parents reported low/normal stress, 34.4% high, and 78.1% very high. In the study by Johnston et al (2003), 25% of mothers of children with FXS felt stress due to isolation and lack of parental competence.…”

“…The main caregivers were either the parents or one parent in the case of 62 patients (82.7%). The fact that in 17 cases (22.7%) there were siblings with FXS means that these families had an additional burden (Haessler et al, 2016).…”

Identifying Atypical Development: A Role of Day-Care Workers?

“…With a benchmark procedure retrospectively analysing home videos of children with FXS, we, among other researchers, demonstrated that these signs can be readily identified and classified by professionals (Zhang et al 2018; see also Baranek et al 2005). Early phenotypes of FXS present a broad spectrum of atypical neurobehavioural features across various domains (e.g., motor, cognition, speech-language, social-communication), which are not specific to FXS (e.g., Haessler et al 2016; Hagerman 2002; Kidd et al 2014; Marschik et al 2014; Raspa et al 2017; Roche et al 2018; Zhang et al 2017). As early signs of FXS overlap with peculiarities of children with other developmental and genetic disorders, to identify these signs requires sensitivity to deviant development in general and not necessarily expertise in a specific syndrome.…”