Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy.

Background: Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinical features of DMD carriers during childhood are poorly known.Patients: We describe...

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Publicado en:Pediatric Neurology Vol. 55; pp. 58 - 64
Autores principales: Papa, Riccardo, Madia, Francesca, Bartolomeo, Domenico, Trucco, Federica, Pedemonte, Marina, Traverso, Monica, Broda, Paolo, Bruno, Claudio, Zara, Federico, Minetti, Carlo, Fiorillo, Chiara
Formato: Journal Article
Publicado: Elsevier B.V. Feb2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2016
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      pub: Elsevier B.V.
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        atl: Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy.
      aug:
        au:
          Papa, Riccardo
          Madia, Francesca
          Bartolomeo, Domenico
          Trucco, Federica
          Pedemonte, Marina
          Traverso, Monica
          Broda, Paolo
          Bruno, Claudio
          Zara, Federico
          Minetti, Carlo
          Fiorillo, Chiara
        affil: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy
      sug:
        subj:
          Muscular Dystrophy, Duchenne
          Muscle Proteins
          Muscular Dystrophy, Duchenne Physiopathology
          Creatine Kinase Blood
          Muscular Dystrophy, Duchenne Pathology
          Muscular Dystrophy, Duchenne Blood
          Prospective Studies
          Child, Preschool
          Female
          Mutation
          Adolescence
          Electromyography
          Child
          Exercise of Self-Care Agency Scale
          Scales
          Child, Preschool: 2-5 years
          Adolescent: 13-18 years
          Child: 6-12 years
          Female
      ab: Background: Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinical features of DMD carriers during childhood are poorly known.Patients: We describe a cohort of pediatric DMD carriers, providing clinical, genetic, and histopathologic features, with a mean follow-up of 7 years.Results: Fifteen females with a DMD mutation (age range 5 to 18 years) were included. Seven patients (46%) presented with clinically evident symptoms and signs such as limb girdle weakness, abnormal gait, and exercise intolerance. The other eight patients (53%) were evaluated because of an incidental finding of elevated level of creatine kinase. Creatine kinase level was elevated in all, ranging from 392 to 13,000 U/L. Calf hypertrophy was observed in eight patients (53%). No patient developed respiratory or cardiac involvement. The most frequent complication was scoliosis (46%). Four patients (29%) also presented minor learning disabilities or behavioral problems. We performed electromyography in half of patients, showing myopathic pattern in four (53%). Muscle biopsy revealed a mosaic reduction of dystrophin in nine available cases. DMD gene mutations were mostly deletions (71%), resulting in loss of reading frame in five patients (36%). The three patients who experienced the most severe disease course were affected either by a nonsense or frameshift mutation.Conclusions: Our analysis suggests that DMD gene mutations may be suspected in a female child with persistently elevated levels of creatine kinase. Evidence of scoliosis, calf hypertrophy, or myopathic pattern at electromyography may also be helpful, and muscle biopsy is always indicative. DMD carriers should be followed for subtle orthopedic and psychiatric complications during childhood.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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