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Phenotypic Variability of Dystrophinopathy Symptomatic Female Carriers

  • Ana Cotta (a1), Julia Filardi Paim (a1), Elmano Carvalho (a2), Mônica Machado Navarro (a3), Jaquelin Valicek (a2), Antonio Lopes da-Cunha-Junior (a4), Miriam Melo Menezes (a5), Simone Vilela Nunes (a5), Rafael Xavier-Neto (a5), Eni Braga da Silveira (a6), Cynthia Costa-e-Silva (a7), Reinaldo Issao Takata (a7) and Antonio Pedro Vargas (a5)...

Abstract

Background: Dystrophinopathies are X-linked muscular dystrophies characterized by pathogenic mutations in the dystrophin gene. Symptomatic dystrophinopathy female carriers may present with limb-girdle weakness. The diagnosis may be challenging in the absence of affected male relatives. We aimed to describe the phenotypic variability in a series of molecular-confirmed female dystrophinopathy patients. Methods: This is a retrospective analysis of medical records from 1997 to 2015. Results: Ten female dystrophinopathy patients were selected, two with unusual phenotypes: one with early joint contractures muscular dystrophy and the other with very late onset myopathy. Muscle imaging studies demonstrated predominant asymmetric fat replacement. Muscle biopsy immunohistochemistry demonstrated clear mosaic pattern in two cases and only subtle reduction of dystrophin intensity in three. Conclusions: Adequate diagnosis is fundamental for genetic counseling and cardiologic follow-up. Female patients with dystrophinopathy may present unusual phenotypes such as early contractures and very late onset myopathy.

Contexte: les dystrophinopathies sont des dystrophies musculaires liées au chromosome X, caracterisées par la mutation pathogénique du gène de la dystrophine. Les femmes porteurs symptomatiques de la dystrophinopathie peuvent présenter une perte de force musculaire proximale. Leur diagnostic peut être un défi en l´absence de membre de la famille de sexe masculin atteind de la dystrophinopathie. L´objectif est décrire la variabilité phénotypique chez une série des femmes atteind de la dystrophinopathie avec la confirmation moléculaire. Méthode: analyse rétrospective des dossiers médicaux depuis 1997 jusqu´a 2015. Résultats: dix femmes avec la dystrophinopathie ont été selectionnés: deux porteurs d´un phénotype atypique: une présentant une contracture articulaire précoce et l´autre une myopathie avec un début très tardif. Les examens d´imagerie de diagnostic des muscles ont démontrés la substitution fibroadipose prédominante asymétrique. L´analyse immunohistochimique de la dystrophine a demontré une claire mosaic chez deux patients et seulement une discrète réduction d´intensité de la dystrophine chez trois patients. Conclusions: le diagnostic adéquat est essentiel pour un conseil génétique et un suivit cardiologic. Les patients présentant une contracture précoce et une myopathie avec un début tardif peuvent être porteurs du phénotype de la dystrophinopathie.

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Corresponding author

Correspondence to: Ana Cotta, Rede SARAH de Hospitais de Reabilitação, Av. Amazonas 5953, Gameleira, 30510-000, Belo Horizonte, MG, Brazil. Email: ana_cotta@yahoo.com.br

References

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Keywords

Phenotypic Variability of Dystrophinopathy Symptomatic Female Carriers

  • Ana Cotta (a1), Julia Filardi Paim (a1), Elmano Carvalho (a2), Mônica Machado Navarro (a3), Jaquelin Valicek (a2), Antonio Lopes da-Cunha-Junior (a4), Miriam Melo Menezes (a5), Simone Vilela Nunes (a5), Rafael Xavier-Neto (a5), Eni Braga da Silveira (a6), Cynthia Costa-e-Silva (a7), Reinaldo Issao Takata (a7) and Antonio Pedro Vargas (a5)...

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