Une opportunité exceptionnelle de créer un outil moderne pour communiquer votre expérience et votre savoir aux autres parents !
Collaboration de plusieurs professionnels mais quoi de plus naturel dès lors que de proposer vos témoignages de parents et/ou de personnes X fragile elles-mêmes !
Une chance extraordinaire d’expliquer le syndrome aux parents, d’évoquer les particularités de ces jeunes tant aux familles qu’aux professionnels de terrain et d’informer le grand public !
Concrétisation de la demande de nombreux parents en recherche des pistes pour leur enfant !
Une chance extraordinaire d’expliquer le syndrome à des parents démunis face au diagnostic. Ce reportage ne peut être que avec vos témoignages de familles !
Comment évoquer les particularités spécifiques de ces enfants et de ces jeunes sans l’avoir vécu ? L’ensemble de ce projet est coordonné par le Pr Lucien Koulischer dont les qualités humaines et scientifiques seront un atout pour sa mission de coordinateur scientifique avec le cinéaste Mourad H. Touati.
Le film est maintenant réalisé et sera diffusé le mercredi 22-04-2020 à Liège : informations ultérieurement …
Le titre retenu est : « X fragile – Au delà des apparances ! »
Comprendre la prémutation X fragile en dehors du FXTAS et de la FXPOI :
Avec une prévalence annoncée de 1 garçon sur 700 et de 1 fille sur 256, nous sommes étonnés de voir si peu de personnes poreuses d’un diagnostic de prémutation X fragile !
Plus grave encore est que si nous prenons note des pourcentages de la population touchées par les FXTAS et FXPOI, nous aurions la moitié des personnes poreuses d’une prémutation qui serait ainsi laissée comme « sans problème » !
Si nous consultons la population en général, le sujet de la prémutation est totalement inconnu !
Si nous consultons la population confrontée au syndrome X fragile, nous sommes devant plusieurs réponses mais très importantes :
– la prémutation n’ a pas d’incidence sur le comportement ni la scolarité …
– la prémutation : c’est pour plus tard quand on sera vieux (50 ans) – c’est à dire le FXTAS …
– la prémutation : c’est un stade intermédiaire et peu sont touchés … il n’y a pas de handicap … mais je crois que le difficultés pour les filles sont nombreuses : dépression, déficit visuo-spatial – fertilité féminine (FXPOI) …
– la prémutation : mon médecin m’a dit de ne pas m’inquiéter maintenant ???
Si nous consultons les professionnels, c’est aussi interpellant :
– la prémutation n’a aucune incidence sur l’avenir …
– la prémutation ne donne pas de handicap (on pourrait être d’accord si on utilise le terme « handicap » au sens légal mais si le terme « handicap » signifie « problèmes comportementaux et/ou cognitifs », une réflexion devrait être menée) …
– la prémutation est très étudiée actuellement : vrai ! Mais on ne parle que de FXTAS (80ù) et un peu de FXPOI …
– la prémutation est un sujet controversé !
Si nous revenons sur l’historique du X fragile depuis la biologie moléculaire, nous retrouvons plusieurs écrits qui nous cite la prémutation avec des troubles différents entre les filles et les garçons avec très peu d’information sur le FXTAS ou la FXPOI. Parmi les symptômes liés à la prémutation, on cite souvent :
– pour les garçons : problèmes en lecture, troubles de l’attention, problèmes de concentration, difficultés en mathématiques, parcours scolaire chaotique … troubles autistiques atypiques …
– pour les filles : problèmes en mathématiques, troubles de l’attention, problèmes de concentration, problèmes de déprime et dépressions, perte de l’estime de soi, parcours scolaire difficile, trouble visuo-spatial, irratabilité extrême, …
Nous sommes convaincus que la prémutation est moins grave que la mutation complète mais qu’elle est loin d’être anodine. Si on revient sur la convention des Nations Unies, chaque personne a le droit de recvoir le sinformations sur son état de santé e de recevoir les soins que celui-ci requiert. La même convention insiste aussi sur l’accompagnement qui doit être adapté à chaque personne en difficultés …
Pourquoi est-il autorisé de ne pas donner le diagnostic, établi et connu du médecin généticien, quand il s’agit de la prémutation ?
Pourquoi l’accompagnement n’est il pas systématisé ? (Il serait possible dans les premières années de la vie de vérifier si effectivement, la prémutation rste sans effet et ne provoqiue pas de retard psychomoteurs ou cognitifs ainsi que des troubles comportmentaux ?)
Pourquoi tant de certitudes pour une situation peu étudiée en dehors du FXTAS et e la FXPOI ?
Le CA de l’Association X fragile – Familles X fragile en Europe
Faites-nous connaitre vos avis par rapport à cette prémutation et dites si vous pensez que sa prévalence (1 garçon/700 et 1 fille/256) vous semble correcte ? Merci … par mail à info@x-fragile.eu
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Conseils pour comprendre et accompagner au quotidien :
Gérald BUSSY, Docteur en psychologie
Recommandations en termes de diagnostic :
méthode fiable et validée – Une information de la Pr Dr Hilde Van ESCH de la KUL Leuven
Dear all,
I would like to comment on the question of Mr Compere regarding this novel test and regarding population screening.
This novel test is one of the many commercially available tests on the market.
However, in all 8 genetic centers in Belgium the classical FMR1 test is done conform guidelines and accreditation. For example in Leuven our diagnostic lab is accredited. There is currently no need to use other commercially available test since population-wide screening is not performed in our country.
In this regard, the clinical working group of the Belgian Society for Human Genetics has provided recommendations for many genetic tests, on request of the High Council. I have attached the document about good clinical practice for FMR1 testing for your reading.
I will not be able to come on 30/11 because I am at a meeting abroad.
Kind regards,
Hilde
prof. dr. Hilde Van Esch
adjunct-kliniekhoofd
centrum menselijke erfelijkheid – center for human genetics
Hilde.VanEsch@uzleuven.be
tel. secr. +32 16 34 59 03 fax +32 16 34 60 51
UZ Leuven| campus Gasthuisberg | Herestraat 49 | B – 3000 Leuven | www.uzleuven.be
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BeSHG Workgroup 29 april 2011-04-28
Clinical indications for FMR-1 analysis
Frequency of Fragile X pre/full mutation.
– males with the full mutation : 1/4000
– women carriers of the premutation : 1/246 to 1/550
– screening children with learning difficulties reveals a ‘new’ case of fragile X syndrome in about 1%
Technology of testing :
The diagnostic procedures are mainly based on southern blotting or on direct amplification of the CGG repeat using flanking primers.
Indications for screening
FMR1 testing is indicated in several clinical situations:
I. Fragile X syndrome:
FMR1 testing is indicated in the evaluation of patients (male and female) with intellectual disability, learning disorder, and/or autism.
FMR1 testing is indicated as part of the first line of the etiological work-up in:
Individuals of either sex with mental retardation, developmental delay, or autism, in the presence of:
(a) physical or behavioral characteristics of fragile X syndrome*.
and/or
(b) a family history of fragile X syndrome, if the pedigree structure indicates that the patient is at risk of inheriting the mutated gene.
and/or
(c) male or female relatives with undiagnosed mental retardation, and a pedigree structure indicating a possible X linked transmission.
*The clinical features of Fragile X are subtle, and there is commonly a delay in making a specific diagnosis.
The degree of impairment can vary from profound handicap through to isolated learning problems but most affected males have a severe to moderate degree of impairment, with IQs in the range of 35–49.
Typical, but not specific behavioural problems include: avoidance of gaze, repetitive mannerism and obsessional traits, hyperactivity, repetitive speech patterns (unusual rhythm and perseverative phraseology).
Physical signs include: large heads for their age (greater than the 50th centile), large ears and a ‘long’ face. Macroorchidism is present only in 20% of prepubertal boys.
FMR1 testing is recommended as part of the etiological work-up in individuals of either sex with mental retardation, developmental delay, or autism. In these situations, FMR1 testing should be performed as part of a comprehensive genetic evaluation that includes cytogenetic analysis (CGH array). Cytogenetic studies are critical, since constitutional chromosome abnormalities have been identified as frequently or more frequently than fragile X mutations in mentally retarded individuals referred for fragile X testing.
II. Premature ovarian failure:
FMR1 testing is indicated for women who have reproductive or fertility problems associated with an elevated level of follicule stimulating hormone (FSH) before the age of 40 years.
Especially, but not only, if they have
(a) a family history of premature ovarian failure, and a pedigree history consistent with an X linked transmission.
and/or
(b) a family history of fragile X syndrome, if the pedigree structure indicates that the patient is at risk of inheriting the mutated gene.
and/or
(c) male or female relatives with undiagnosed mental retardation and a pedigree structure indicating a possible X-linked transmission.
III. Tremor/ataxia syndrome (FXTAS):
FMR1 testing is indicated in men and women who are experiencing late onset intention tremor and cerebellar ataxia of unknown origin, especially if they have
(a) a family history of movement disorders, and a pedigree structure consistent with an X linked transmission.
and/or
(b) a family history of fragile X syndrome, if the pedigree structure indicates that the patient is at risk of inheriting the mutated gene.
and/or
(c) male or female relatives with undiagnosed mental retardation, and a pedigree structure consistent with an X-linked transmission
and/or
(d) a brain MRI suggestive of FXTAS (white matter lesions in the middle cerebellar peduncles and/or brain stem)
IV. Genetic counselling :
1) Individuals seeking reproductive counselling:
(a) Fragile X testing is indicated for a woman with a family history of fragile X syndrome, fragile X tremor/ataxia syndrome, or premature ovarian failure (in more than one family member) if the pedigree structure indicates that she is at risk of inheriting the mutated gene. Referral to a medical geneticist for counselling and assessment should be considered in these cases.
(b) Fragile X testing is indicated for a woman with a family history of undiagnosed mental retardation, if the pedigree structure is consistent with an X-linked transmission, and is indicating that the patient is at risk of inheriting the mutated gene.
2) Foetuses of known carrier mothers.
Prenatal fetal testing via chorionic villus sampling or amniocentesis should be offered to women who are confirmed to be carriers of a premutation or full mutation of the FMR-1 gene.
Ideally DNA testing should be performed on cultured amniocytes obtained by amniocentesis after 14 weeks’ gestation, but in this case the result is available around 18 weeks’gestation. DNA testing can be performed on chorionic villi obtained by CVS at 10 to 12 weeks’ gestation, but the results must be interpreted with caution because the methylation status of the FMR1 gene is often not yet established in chorionic villi at the time of sampling. A follow-up amniocentesis may be necessary to resolve an ambiguous result.
3) “Cascade counselling”.
FMR1 testing should be offered to relatives of carriers of an FMR1 full-or premutation.
Simulations indicate that case-finding and cascade counselling can reach about half of the premutation carriers, if index cases in the family were used as starting points and testing extended to fifth-degree relatives. If performed in the case of a full FMR1 mutation, identified carrier would include most of those at the highest risk of having a child with fragile X syndrome, as permutation in these families has demonstrated its unstability.
Cascade counselling should be performed by a medical geneticist. Individuals should be tested at an appropriate life stage.
4) Population screening
Population carrier screening is not recommended at this time, except as part of a well-defined clinical research protocol.
While the DNA test is very accurate, two issues limit the application of FMR1 testing as a general prenatal population screening.
a. An uncertainty remains about the risks for women from the general population with FMR1 premutation with 55–65 CGG repeats. 30% of woman identified with an FMR1 permutation have CGG repetition between 56-65 (in a study where woman with CGG repetition between 50 and 55 account for 40% of the identified permutation carriers (Toledano-Alhadef et al)). The repartition of the number of CGG repeat in this population, and its low but uncertain risk of expansion to a full mutation might lead to a high number of undue prenatal testing.
Considerable work must be done before instituting general population screening protocols regarding identification and management of intermediate allele carriers.
b. The nature of different phenotypes associated with the FMR1 mutation in its premutation and full mutation forms and the inheritance pattern are complex, the approach to genetic counseling for different phenotypes including early onset disorder of mental retardation, adult onset of premature ovarian failure, and a late onset disorder associated with neurodegeneration, all within the same family has not yet been addressed at a clinical level much less a population screening level.
References :
Pembrey ME, Barnicoat AJ, Carmichael B, Bobrow M, Turner G. An assessment of screening strategies for fragile X syndrome in the UK. Health Technol Assess. 2001;5(7):1-95.
Allyn McConkie-Rosell,Brenda Finucane,Amy Cronister,Liane Abrams,Robin L. Bennett,and Barbara J. Pettersen. Genetic Counseling for Fragile X Syndrome: Updated Recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 2005. Vol. 14, No. 4. 249-70.
Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. 2005 Oct;7(8):584-7.
Chitayat D, Wyatt PR, Wilson RD, Johnson JA, Audibert F, Allen V, Gagnon A, Langlois S, Blight C, Brock JA, Désilets V, Farell SA, Geraghty M, Nelson T, Nikkel SM, Skidmore D,Shugar. Fragile X testing in obstetrics and gynaecology in Canada. AJ Obstet Gynaecol Can. 2008 Sep;30(9):837-46.
Toledano-Alhadef H, Basel-Vanagaite L, Magal N, Davidov B, Ehrlich S, Drasinover V, Taub E, Halpern GJ, Ginott N, Shohat M. Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. Am J Hum Genet. 2001 Aug;69(2):351-60. Epub 2001 Jul 6.
Nolin SL, Dobkin C, Brown WT Molecular analysis of fragile X syndrome. Curr Protoc Hum Genet.2003 Nov;Chapter 9:Unit9.5.