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.

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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

Differences in Characteristics Among New Pediatric Neurology Patients: The Effect of a Newly Established Private Pediatric Neurology Practice

Differences in Characteristics Among New Pediatric Neurology Patients: The Effect of a Newly Established Private Pediatric Neurology Practice

Jeanne Van Cleave, MD, Brian Woodruff, MD, Gary L. Freed, MD, MPH

Received 25 July 2006; accepted 6 November 2007.

Objective

To investigate changes in volume and characteristics of new patients referred when a private pediatric neurology practice (PP) opened in 2004 in an area served primarily by an academic medical center's (AMC) pediatric neurology practice.

Methods

Retrospective analysis of medical and billing records to examine changes in volume, diagnosis, and sociodemographic factors of new patients at the AMC from July 2004 to June 2005; the PP during the same period; and the AMC during the year before.

Results

One year after the PP opened, 40% more new pediatric neurology patients were seen in this area than the year before. Compared with the AMC, PP saw a greater proportion of seizures (34% vs 26%, P < .05) and headaches (32% vs 17%, P < .001), and a lesser proportion of developmental delay/musculoskeletal disorders (12% vs 19%, P < .001) and congenital/metabolic disorders (<1%>P < .001). Fewer PP patients lived >20 miles from the practice (32% vs 64%, P < .001), and fewer had public insurance (4% vs 33%, P < .001).

Conclusions

The establishment of the PP dramatically increased the volume of new pediatric neurology patients in this area. After the PP opened, the AMC continued to care for most patients with rare diseases and fewer financial resources. Future research should examine whether the increase in volume reflects relief of pent-up demand or increased referral rates due to eased access, and should elucidate how differences in patient populations at academic and private subspecialty practices relate to access to subspecialty care and financial well-being of academic practices.

Key Words: academic medical center, pediatric neurology, private practice, referral, consultation