Tremor-Ataxia Syndrome and Primary Ovarian Insufficiency in an FMR1 Premutation Carrier
Article Sidebar
Main Article Content
Introduction:
The FMR1 gene has four allelic variants according to the number of repeats of the CGG triplet. Premutation carriers with between 55 and 200 repeats are susceptible to developing pathologies such as tremor and ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) syndrome.
Case description:
The patient was a 53-year-old female farmer with severe tremor in the upper limbs at rest that worsens with movement, tremor in the jaw and tongue, and generalized cerebral atrophy. She is a carrier of the FMR1 premutation diagnosed by PCR and Southern Blot, complying with the clinical and radiological criteria of FXTAS, and in addition, has a history of vagal symptoms suggestive of ovarian failure and menstrual cycle disorders that led to hysterectomy at age 33 and was subsequently diagnosed with FXPOI.
Conclusion:
An unusual case of FXTAS and FXPOI complying with clinical and radiological criteria is reported in a premutation carrier of the FMR1 gene.
- Síndrome de temblor y ataxia X fragil
- complicaciones/ataxia
- diagnostico/ataxia
- genetica/ataxia
- FXPOI
- FXTAS
- gen FMR1.
Online Mendelian Inheritance in Man. An Online Catalog of Human Genes and Genetic Disorders. Entry - # 300624 - Fragile X Mental Retardation Syndrome. Cited: 2014 Aug 31. Available from: http://www.omim.org/entry/300624.
Saldarriaga W, Tassone F, González-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R. Síndrome de X Frágil. Colomb Med (Cali). 2014; 45(4): 190-8. DOI: https://doi.org/10.25100/cm.v45i4.1810
Hagerman RJ, Hagerman P. Fragile X-associated tremor/ataxia syndrome - features, mechanisms and management. Nat Rev Neurol. 2016; 12(7): 403-12. DOI: https://doi.org/10.1038/nrneurol.2016.82
Pirozzi F, Tabolacci E, Neri G. The FRAXopathies: Definition, overview, and update. Am J Med Genet A. 2011; 155A(8): 1803-16. DOI: https://doi.org/10.1002/ajmg.a.34113
Saldarriaga W, Lein P, González TLY, Isaza C, Rosa L, Polyak A, et al. Phenobarbital use and neurological problems in FMR1 premutation carriers. Neurotoxicology. 2016; 53: 141-7. DOI: https://doi.org/10.1016/j.neuro.2016.01.008
Faher S, Tolosa E, Marin C. Clinical rating scale for tremor. En: Jankovic J, Tolosa E. Parkinson´s Disease and Movement Disorder. Baltimore: Urban & Schwarzenberg. 1988. p:225-34.
Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Internal Med. 2006; 166(10): 1092-7. DOI: https://doi.org/10.1001/archinte.166.10.1092
Hunter J, Rivero-Arias O, Angelov A, Kim E, Fotheringham I, Leal J. Epidemiology of fragile X syndrome: A systematic review and meta-analysis. Am J Med Genet A. 2014; 164A(7): 1648-58. DOI: https://doi.org/10.1002/ajmg.a.36511
Grigsby J, Brega AG, Bennett RE, Bourgeois JA, Seritan AL, Goodrich GK, et al. Clinically significant psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, and the mediating influence of executive functioning. Clin Neuropsychol. 2016; 30(6): 944-59. DOI: https://doi.org/10.1080/13854046.2016.1185100
Cordeiro L, Abucayan F, Hagerman R, Tassone F, Hessl D. Anxiety disorders in fragile X premutation carriers: Preliminary characterization of probands and non-probands. Intractable Rare Dis Res. 2015; 4(3): 123-30. DOI: https://doi.org/10.5582/irdr.2015.01029
Grigsby J, Brega AG, Bennett RE, Bourgeois JA, Seritan AL, Goodrich GK, et al. Clinically significant psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, and the mediating influence of executive functioning. Clin Neuropsychol. 2016; 30(6): 944-59. DOI: https://doi.org/10.1080/13854046.2016.1185100
Lozano R, Saito N, Reed D, Eldeeb M, Schneider A, Hessl D, et al. Aging in Fragile X Premutation Carriers. Cerebellum. 2016; 15(5): 587-94. DOI: https://doi.org/10.1007/s12311-016-0805-x
Chonchaiya W, Au J, Schneider A, Hessl D, Harris SW, Laird M, et al. Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder. Hum Genet. 2012; 131(4): 581-9. DOI: https://doi.org/10.1007/s00439-011-1106-6
Welt CK, Smith PC, Taylor AE. Evidence of early ovarian aging in fragile X premutation carriers. J Clin Endocrinol Metab. 2004; 89(9): 4569-74. DOI: https://doi.org/10.1210/jc.2004-0347
Wheeler AC, Raspa M, Green A, Bishop E, Bann C, Edwards A, et al. Health and reproductive experiences of women with an FMR1 premutation with and without fragile X premature ovarian insufficiency. Front Genet. 2014; 5: 300. DOI: https://doi.org/10.3389/fgene.2014.00300
Sherman SL, Allen EG, Spencer JB, Nelson LM. Clinical manifestation and management of FXPOI. In: Tassone F, Hall DA, editors. FXTAS, FXPOI, and Other Premutation Disorders. Second. Switzerland: Springer; 2016. pp 199-224. DOI: https://doi.org/10.1007/978-3-319-33898-9_10
Sethna F, Moon C, Wang H. From FMRP function to potential therapies for fragile X syndrome. Neurochem Res. 2014; 39(6): 1016-31. DOI: https://doi.org/10.1007/s11064-013-1229-3
Usdin K, Hukema RK, Sherman SL. Model systems for understanding FXPOI. In: Tassone F, Hall DA (eds). FXTAS, FXPOI, and Other Premutation Disorders. second. Switzerland: Springer; 2016. p. 225-40. DOI: https://doi.org/10.1007/978-3-319-33898-9_11
Hall DA, Berry-Kravis E, Hagerman RJ, Hager- Man PJ, Rice CD, Leehey MA. Symptomatic treatment in the fragile X-associated tremor/ataxia syndrome. Mov Disord. 2006; 21(10): 1741-4.. DOI: https://doi.org/10.1002/mds.21001
Downloads
- Harry Castillo-Plata, Nelson Rivera-Franco, Claudia Valencia-Peña, Wilmar Saldarriaga-Gil, Lyle Newball, Andres Castillo Giraldo, Preliminary identification of pathogenic variants in an afro-Colombian raizal family with risk factors for glaucoma , Colombia Medica: Vol. 53 No. 2 (2022)
- Wilmar Saldarriaga-Gil, Fabian Andres Ruiz-Murcia, Andres Fandiño-Losada, Manuel Enrique Cruz-Perea, Carolina Isaza-de-Lourido, Evaluation of prenatal diagnosis of congenital defects by screening ultrasound, in Cali, Colombia. , Colombia Medica: Vol. 45 No. 1 (2014)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use