Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2016

Open Access 01-12-2016 | Research article

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

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

Published in: BMC Psychiatry | Issue 1/2016

Login to get access

Abstract

Background

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.

Methods

EXPLAIN-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.

Results

Seventy-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).

Conclusions

This 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 registration

The ClinTrials.gov identifier is NCT01711606. Registered on 18 October 2012.
Literature
1.
Carter MT, Scherer SW. Autism spectrum disorder in the genetics clinic: a review. Clin Genet. 2013;83(5):399–407.CrossRefPubMed
2.
3.
Sofocleous C, Kolialexi A, Mavrou A. Molecular diagnosis of Fragile X syndrome. Expert Rev Mol Diagn. 2009;9(1):23–30.CrossRefPubMed
4.
Lewis P, Abbeduto L, Murphy M, Richmond E, Giles N, Bruno L, et al. Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism. J Intellect Disabil Res. 2006;50(Pt 7):532–45.CrossRefPubMed
5.
Barnes E, Roberts J, Long SH, Martin GE, Berni MC, Mandulak KC, et al. Phonological accuracy and intelligibility in connected speech of boys with fragile X syndrome or Down syndrome. J Speech Lang Hear Res. 2009;52(4):1048–61.CrossRefPubMedPubMedCentral
6.
Deshpande PS, Coffey DB. Fragile X syndrome and attention-deficit/hyperactivity disorder symptoms. J Child Adolesc Psychopharmacol. 2011;21(6):639–42.CrossRefPubMedPubMedCentral
7.
Sansone SM, Widaman KF, Hall SS, Reiss AL, Lightbody A, Kaufmann WE, et al. Psychometric study of the Aberrant Behavior Checklist in Fragile X Syndrome and implications for targeted treatment. J Autism Dev Disord. 2012;42(7):1377–92.CrossRefPubMedPubMedCentral
8.
McCary LM, Roberts JE. Early identification of autism in fragile X syndrome: a review. J Intellect Disabil Res. 2013;57(9):803–14.CrossRefPubMed
9.
Gabis LV, Baruch YK, Jokel A, Raz R. Psychiatric and autistic comorbidity in fragile X syndrome across ages. J Child Neurol. 2011;26(8):940–8.CrossRefPubMed
10.
Sabaratnam M, Murthy NV, Wijeratne A, Buckingham A, Payne S. Autistic-like behaviour profile and psychiatric morbidity in Fragile X Syndrome: a prospective ten-year follow-up study. Eur Child Adolesc Psychiatry. 2003;12(4):172–7.CrossRefPubMed
11.
Berry-Kravis E, Raspa M, Loggin-Hester L, Bishop E, Holiday D, Bailey DB. Seizures in fragile X syndrome: characteristics and comorbid diagnoses. Am J Intellect Dev Disabil. 2010;115(6):461–72.CrossRefPubMed
12.
13.
Berry-Kravis E, Potanos K. Psychopharmacology in fragile X syndrome--present and future. Ment Retard Dev Disabil Res Rev. 2004;10(1):42–8.CrossRefPubMed
14.
Bailey Jr DB, Raspa M, Bishop E, Olmsted M, Mallya UG, Berry-Kravis E. Medication utilization for targeted symptoms in children and adults with fragile X syndrome: US survey. J Dev Behav Pediatr. 2012;33(1):62–9.CrossRefPubMed
15.
Martin GE, Ausderau KK, Raspa M, Bishop E, Mallya U, Bailey Jr DB. Therapy service use among individuals with fragile X syndrome: findings from a US parent survey. J Intellect Disabil Res. 2013;57(9):837–49.CrossRefPubMed
16.
Moskowitz LJ, Jones EA. Uncovering the evidence for behavioral interventions with individuals with fragile X syndrome: a systematic review. Res Dev Disabil. 2015;38:223–41.CrossRefPubMed
17.
Stasolla F, Damiani R, Perilli V, Di Leone A, Albano V, Stella A, et al. Technological supports to promote choice opportunities by two children with fragile X syndrome and severe to profound developmental disabilities. Res Dev Disabil. 2014;35(11):2993–3000.CrossRefPubMed
18.
Stasolla F, Perilli V, Damiani R, Albano V. Assistive technology to promote occupation and reduce mouthing by three boys with fragile X syndrome. Dev Neurorehabil. 2016: 1-9. Epub ahead of print.
19.
20.
Levenga J, Hayashi S, de Vrij FM, Koekkoek SK, van der Linde HC, Nieuwenhuizen I, et al. AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiol Dis. 2011;42(3):311–7.CrossRefPubMed
21.
Haessler F, Gaese F, Colla M, Huss M, Kretschmar C, Brinkman M, et al. EXPLAIN Fragile-X: an explorative, longitudinal study on the characterization, treatment pathways, and patient-related outcomes of Fragile X Syndrome. BMC Psychiatry. 2013;13:339.CrossRefPubMedPubMedCentral
22.
23.
24.
Giangreco CA, Steele MW, Aston CE, Cummins JH, Wenger SL. A simplified six-item checklist for screening for fragile X syndrome in the pediatric population. J Pediatr. 1996;129(4):611–4.CrossRefPubMed
25.
Derogatis LR, Lipman RS, Covi L. SCL-90: an outpatient psychiatric rating scale--preliminary report. Psychopharmacol Bull. 1973;9(1):13–28.PubMed
26.
Kuhl HC, Hartwig I, Petitjean S, Muller-Spahn F, Margraf J, Bader K. Validation of the Symptom Checklist SCL-27 in psychiatric patients: Psychometric testing of a multidimensional short form. Int J Psychiatry Clin Pract. 2010;14(2):145–9.CrossRefPubMed
27.
Kubinger K. The intelligence test-battery AID 2 as a prototypical globalized test. Test Int. 2008;19:13–4.
28.
Petermann F, Petermann U. HAWIK-IV. 3rd ed. Bern: Huber Verlag; 2010.
29.
Melchers P, Preuß U. Kaufman Assessment Battery for Children. Eightsth ed. Frankfurt/Main: Pearson Assessment; 2009.
30.
Harris S. An evaluation of the Snijders-Oomen nonverbal intelligence scale for young children. J Pediatr Psychol. 1982;7(3):239–51.CrossRefPubMed
31.
Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985;89(5):485–91.PubMed
32.
Newton JT, Sturmey P. The Aberrant Behaviour Checklist: a British replication and extension of its psychometric properties. J Ment Defic Res. 1988;32(Pt 2):87–92.PubMed
33.
Greiner W, Claes C, Busschbach JJ, von der Schulenburg JM. Validating the EQ-5D with time trade off for the German population. Eur J Health Econ. 2005;6(2):124–30.CrossRefPubMed
34.
Wille N, Badia X, Bonsel G, Burstrom K, Cavrini G, Devlin N, et al. Development of the EQ-5D-Y: a child-friendly version of the EQ-5D. Qual Life Res. 2010;19(6):875–86.CrossRefPubMedPubMedCentral
35.
Loyd BH, Abidin RR. Revision of the parenting stress index. J Pediatr Psychol. 1985;10(2):169–77.CrossRefPubMed
36.
Honigfeld G. NOSIE--30: history and current status of its use in pharmacopsychiatric research. Mod Probl Pharmacopsychiatry. 1974;7:238–63.CrossRefPubMed
37.
Honigfeld G, Gillis RD, Klett CJ. NOSIE-30: a treatment-sensitive ward behavior scale. Psychol Rep. 1966;19(1):180–2.CrossRefPubMed
38.
Linden M, Baron S, Muschalla B. Mini-ICF-Rating für Aktivitäts- und Partizipationsstörungen bei psychischen Erkrankungen. Bern: Hans Huber Verlag; 2009.
39.
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7.CrossRef
40.
Hartley SL, Wheeler AC, Mailick MR, Raspa M, Mihaila I, Bishop E, et al. Autism symptoms across adulthood in men with Fragile X syndrome: a cross-sectional analysis. J Autism Dev Disord. 2015;45(11):3668–79.CrossRefPubMedPubMedCentral
41.
Gomez-Mancilla B, Berry-Kravis E, Hagerman R, von Raison F, Apostol G, Ufer M, et al. Development of mavoglurant and its potential for the treatment of fragile X syndrome. Expert Opin Investig Drugs. 2014;23(1):125–34.CrossRefPubMed
42.
Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, et al. Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci Transl Med. 2016;8(321):321ra5.CrossRefPubMed
43.
Berry-Kravis EM, Hessl D, Rathmell B, Zarevics P, Cherubini M, Walton-Bowen K, et al. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci Transl Med. 2012;4(152):152ra27.CrossRef
44.
Emerson E, Einfeld S, Stancliffe RJ. The mental health of young children with intellectual disabilities or borderline intellectual functioning. Soc Psychiatry Psychiatr Epidemiol. 2010;45(5):579–87.CrossRefPubMed
45.
Gallagher A, Hallahan B. Fragile X-associated disorders: a clinical overview. J Neurol. 2012;259(3):401–13.CrossRefPubMed
46.
Hartley SL, Seltzer MM, Raspa M, Olmstead M, Bishop E, Bailey DB. Exploring the adult life of men and women with fragile X syndrome: results from a national survey. Am J Intellect Dev Disabil. 2011;116(1):16–35.CrossRefPubMedPubMedCentral
47.
Habetaler F, Thome J, Reis O. Polypharmacy in the treatment of subjects with intellectual disability. J Neural Transm (Vienna). 2015;122 Suppl 1:S93–S100.CrossRef
48.
Young NJ, Findling RL. An update on pharmacotherapy for autism spectrum disorder in children and adolescents. Curr Opin Psychiatry. 2015;28(2):91–101.
49.
Hässler F, Reis O. Pharmacotherapy of disruptive behavior in mentally retarded subjects: A review of the current literature. Dev Disabil Res Rev. 2010;16(3):265–72.CrossRefPubMed
50.
Wang H, Pati S, Pozzo-Miller L, Doering LC. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes. Front Cell Neurosci. 2015;9:55.PubMedPubMedCentral
51.
52.
Morfeld M, Bullinger M, Nantke J, Brahler E. The version 2.0 of the SF-36 Health Survey: results of a population-representative study. Soz Praventivmed. 2005;50(5):292–300.CrossRefPubMed
53.
Noyes J, Edwards RT. EQ-5D for the assessment of health-related quality of life and resource allocation in children: a systematic methodological review. Value Health. 2011;14(8):1117–29.CrossRefPubMed
54.
55.
Kidd SA, Lachiewicz A, Barbouth D, Blitz RK, Delahunty C, McBrien D, et al. Fragile X syndrome: a review of associated medical problems. Pediatrics. 2014;134(5):995–1005.CrossRefPubMed
Metadata
Title
Characterization, treatment patterns, and patient-related outcomes of patients with Fragile X syndrome in Germany: final results of the observational EXPLAIN-FXS study
Authors
Frank Haessler
Franziska Gaese
Michael Huss
Christoph Kretschmar
Marc Brinkman
Helmut Peters
Samuel Elstner
Michael Colla
David Pittrow
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2016
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-016-1020-5

Other articles of this Issue 1/2016

BMC Psychiatry 1/2016 Go to the issue

Research article

Brain volumes and regional cortical thickness in young females with anorexia nervosa

Research article

Clinical characteristics of patients assessed within an Improving Access to Psychological Therapies (IAPT) service: results from a naturalistic cohort study (Predicting Outcome Following Psychological Therapy; PROMPT)

Research Article

Co-occurring symptoms of attention deficit hyperactivity disorder (ADHD) in a population-based sample of adolescents screened for depression

Research article

Concepts of madness in diverse settings: a qualitative study from the INTREPID project

Research article

Experiences of support in working toward personal recovery goals: a collaborative, qualitative study

Research article

Differential impact of parental region of birth on negative parenting behavior and its effects on child mental health: Results from a large sample of 6 to 11 year old school children in France