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Mov Disord. 2016 Jan;31(1):62-9. doi: 10.1002/mds.26382. Epub 2015 Sep 21.

Delayed-onset Friedreich's ataxia revisited.

Author information

1
Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France.
2
Département de Génétique et Cytogénétique, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France.
3
Département de Neurologie et Pathologie du mouvement, Hôpital de la Timone, Marseille, France.
4
Université De Bordeaux, Institut des Maladies Neurodégénératives, CNRS UMR 5293, Bordeaux, France; and Département de Neurologie, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.
5
Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles (ULB), Brussels, Belgium.
6
Laboratoire d'Explorations Fonctionnelles, Centre de Référence Maladies Neuromusculaires Nantes-Angers, Hôtel-Dieu, CHU Nantes, Nantes, France.
7
Département de Neurologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France.
8
Département de Neurologie, Hôpital Emile-Muller, Mulhouse, France.
9
Service de Neurophysiologie, Hôpital Charles-Nicolle, CHU de Rouen, Rouen, France.
10
Département de Neurologie, CHU de Brest, Brest, France.
11
Département de Neurologie, Hôpital GR Laënnec, CHU de Nantes, Nantes, France.
12
UPMC Université Paris 06, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, CNRS 7225, Hôpital de la Pitié-Salpêtrière, Paris, France; and INSERM, UMR_S975, Paris, France.
13
CHU Bordeaux, Service de Génétique Médicale, Université Bordeaux, Laboratoire Maladies Rares: Génétique et Métabolisme (MRGM), EA4576, Bordeaux, France.
14
Département de Neurologie, Hôpital Purpan, CHU de Toulouse, Toulouse, France; and Service de Génétique Médicale, Hôpital Purpan, CHU de Toulouse, Toulouse, France.
15
Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU Montpellier, Montpellier, France.
16
Département de Génétique et Cytogénétique, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; UPMC Université Paris 06, UMR_S975, Centre de Recherche Institut du Cerveau et de la Moelle, CNRS 7225, Hôpital de la Pitié-Salpêtrière, Paris, France; and INSERM, UMR_S975, Paris, France.
17
Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU Montpellier, France; and Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France.
18
Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles (ULB), Brussels, Belgium; and Département de Neurologie, Hôpital Erasme, Brussels, Belgium.
19
Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France; and Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
20
Département de Neurologie, Hôpital de Hautepierre, CHU de Strasbourg, France Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch, France; and Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.

Abstract

BACKGROUND:

Friedreich's ataxia usually occurs before the age of 25. Rare variants have been described, such as late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, occurring after 25 and 40 years, respectively. We describe the clinical, functional, and molecular findings from a large series of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia and compare them with typical-onset Friedreich's ataxia.

METHODS:

Phenotypic and genotypic comparison of 44 late-onset Friedreich's ataxia, 30 very late-onset Friedreich's ataxia, and 180 typical Friedreich's ataxia was undertaken.

RESULTS:

Delayed-onset Friedreich's ataxia (late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia) had less frequently dysarthria, abolished tendon reflexes, extensor plantar reflexes, weakness, amyotrophy, ganglionopathy, cerebellar atrophy, scoliosis, and cardiomyopathy than typical-onset Friedreich's ataxia, along with less severe functional disability and shorter GAA expansion on the smaller allele (P < 0.001). Delayed-onset Friedreich's ataxia had lower scale for the assessment and rating of ataxia and spinocerebellar degeneration functional scores and longer disease duration before wheelchair confinement (P < 0.001). Both GAA expansions were negatively correlated to age at disease onset (P < 0.001), but the smaller GAA expansion accounted for 62.9% of age at onset variation and the larger GAA expansion for 15.6%. In this comparative study of late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia, no differences between these phenotypes were demonstrated.

CONCLUSION:

Typical- and delayed-onset Friedreich's ataxia are different and Friedreich's ataxia is heterogeneous. Late-onset Friedreich's ataxia and very-late-onset Friedreich's ataxia appear to belong to the same clinical and molecular continuum and should be considered together as "delayed-onset Friedreich's ataxia." As the most frequently inherited ataxia, Friedreich's ataxia should be considered facing compatible pictures, including atypical phenotypes (spastic ataxia, retained reflexes, lack of dysarthria, and lack of extraneurological signs), delayed disease onset (even after 60 years of age), and/or slow disease progression.

KEYWORDS:

Friedreich's ataxia; corticospinal tract; genetics; imaging; peripheral neuropathy

PMID:
26388117
DOI:
10.1002/mds.26382
[Indexed for MEDLINE]

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