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

Frank Haessler,Marc Brinkman,Franziska Gaese,David Pittrow,Christoph Kretschmar,Michael Colla,Helmut Peters,Michael Huss,Samuel Elstner

doi:10.1186/s12888-016-1020-5

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.

Highlights

As 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
It is caused by expansion of a cytosine-guanine-guanine (CGG) triplet repeat in the fragile mental retardation 1 (FMR1) gene located on the X chromosome
While both males and females can be affected by FXS, in females, the rates of explicit disease are much lower, and symptoms often milder, due to the inactivation of only one of the two X chromosomes in female cells

Summary

Introduction

As 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. The presence of more than 200 repeats in the full mutation - compared with 6-44 repeats in normal individuals – is associated with complete or partial absence of the fragile mental retardation protein (FMRP), which regulates neurotransmitter-activated dendritic translation and synaptic plasticity [2]. While both males and females can be affected by FXS, in females, the rates of explicit disease are much lower, and symptoms often milder, due to the inactivation of only one of the two X chromosomes in female cells (all females with FXS are mosaic by definition). Every sixth child with FXS suffers from seizures [11]

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