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

BACKGROUND:Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, developmuscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinicalfeatures of DMD carriers during childhood are poorly known.PATIENTS:We describe a cohort of pediatric DMDcarriers, providing clinical, genetic, and histopathologic features, with a mean follow-up of 7 years.RESULTS:Fifteenfemales with a DMD mutation (age range 5 to 18 years) were included. Seven patients (46%) presented withclinically evident symptoms and signs such as limb girdle weakness, abnormal gait, and exercise intolerance. Theother eight patients (53%) were evaluated because of an incidentalfinding 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 eightpatients (53%). No patient developed respiratory or cardiac involvement. The most frequent complication wasscoliosis (46%). Four patients (29%) also presented minor learning disabilities or behavioral problems. We performedelectromyography in half of patients, showing myopathic pattern in four (53%). Muscle biopsy revealed a mosaicreduction of dystrophin in nine available cases. DMD gene mutations were mostly deletions (71%), resulting in lossof reading frame infive patients (36%). The three patients who experienced the most severe disease course wereaffected either by a nonsense or frameshift mutation.CONCLUSIONS:Our analysis suggests that DMD gene mutationsmay be suspected in a female child with persistently elevated levels of creatine kinase. Evidence of scoliosis, calfhypertrophy, 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