title: Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Papa
authors.affiliation: Laboratory of Neurogenetics and Neuroscience, Istituto G.Gaslini, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Madia
authors.affiliation: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Bartolomeo
authors.affiliation: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Trucco
authors.affiliation: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pedemonte
authors.affiliation: Laboratory of Neurogenetics and Neuroscience, Istituto G.Gaslini, Genoa, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Traverso
authors.affiliation: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Broda
authors.affiliation: Centre of Myology and Neurodegenerative Disorders, Istituto G.Gaslini, Genoa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.affiliation: Laboratory of Neurogenetics and Neuroscience, Istituto G.Gaslini, Genoa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.affiliation: Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy; DINOGMI, University of Genoa, Genoa, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.affiliation: DINOGMI, University of Genoa, Genoa, Italy. Electronic address: chi.fiorillo@gmail.com.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorillo
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood*; D016189:Dystrophin / Q000235:genetics*; D004576:Electromyography; D005260:Female; D005500:Follow-Up Studies; D016368:Frameshift Mutation; D006801:Humans; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D017384:Sequence Deletion
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D003402:Creatine Kinase
keywords: Duchenne muscular dystrophy; female carrier; pediatric