FRAXTAS in women inherited from mother

FRAXTAS paper in Neurology October 2010

Motor and mental dysfunction in mother–daughter transmitted FXTAS

L. Rodriguez-Revenga, BS, PhD, J. Pagonabarraga, MD, PhD, B. Gómez-Anson, MD, PhD, FRCR, O. López-Mourelo, BS, I. Madrigal, BS, PhD, M. Xunclà, BS, J. Kulisevsky, MD, PhD and M. Milà, BS, PhD From the CIBER de Enfermedades Raras (CIBERER) (L.R.-R., I.M., M.M.), Barcelona; Biochemistry and Molecular Genetics Department (L.R.-R., I.M., M.X., M.M.), Hospital Clínic, Barcelona; Neurology Service (J.P., J.K.) and Neuroradiology Unit, Radiology Department (B.G.-A.), Hospital Sant Pau, Barcelona; CIBER de Enfermedades Neurodegenerativas (CIBERNED) (J.P., B.G.-A., J.K.), Barcelona; Fundació de Recerca Hospital Sant Pau (O.L.-M.), Barcelona; PIC (O.L.-M.), IFAE, Universitat Autonoma Barcelona; Fundació Clínic per a la Recerca Biomèdica (M.X.), Barcelona; and IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (M.M.), Barcelona, Spain.
Address correspondence and reprint requests to Dr. Montserrat Milà, Biochemistry and Molecular Genetics Service, Hospital Clínic, C/Villarroel, 170, 08036 Barcelona, Spain mmila@clinic.ub.es
Objectives: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neuropsychiatric degenerative disorder that occurs predominantly in male FMR1 premutation carriers. Recently, a broader FXTAS spectrum that, besides the core features of tremor and gait ataxia, also includes neuropsychiatric symptoms and neuropathy as further clinically relevant symptoms has been described among females. Herein 2 fragile X syndrome families with a mother–daughter FXTAS transmission are described in detail in order to shed more light on the female FXTAS phenotype.
Methods: Molecular characterization included CGG repeat length, X-chromosome inactivation pattern determination, as well as FMR1 mRNA and FMRP levels quantification. Neuroradiologic examination was performed by 3-T MRI. Neuropsychological assessment included global cognitive, attention, and executive prefrontal functions, verbal fluencies, verbal memory, and visuospatial perception.
Results: Molecular, neurologic, neuropsychiatric, psychological, cognitive, and neuroradiologic features description of 2 fragile X syndrome families with a mother–daughter FXTAS transmission in which dementia is present in both mothers.
Conclusions: Although it is not yet clear to what extent FXTAS shortens lifespan, our findings show that FXTAS progresses from mild tremor and/or ataxia to disabling motor and cognitive impairment, compromising the patients' quality of life. Furthermore, our results show that FXTAS in women can also develop as a multisystem neurodegenerative disorder with central and peripheral nervous system involvement, and both motor and mental disturbances.

---

Study funding: Supported by MARATO TV3 (TV06-0810), FIS 07-0770, and FIS 09-00413.

Received February 26, 2010 Accepted in final form June 28, 2010