Riccardo Papa1, Francesca Madia2, Domenico Bartolomeo1, Federica Trucco1, Marina Pedemonte1, Monica Traverso2, Paolo Broda1, Claudio Bruno3, Federico Zara2, Carlo Minetti4, Chiara Fiorillo5. 1. Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy. 2. Laboratory of Neurogenetics and Neuroscience, Istituto G.Gaslini, Genoa, Italy. 3. Centre of Myology and Neurodegenerative Disorders, Istituto G.Gaslini, Genoa, Italy. 4. Paediatric Neurology and Neuromuscular Disorders Unit, Istituto G. Gaslini, Genoa, Italy; DINOGMI, University of Genoa, Genoa, Italy. 5. DINOGMI, University of Genoa, Genoa, Italy. Electronic address: chi.fiorillo@gmail.com.
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. 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.
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.
Authors: Josef Finsterer; Claudia Stöllberger; Birgit Freudenthaler; Desiree De Simoni; Romana Höftberger; Klaus Wagner Journal: Intractable Rare Dis Res Date: 2018-05
Authors: Vladimír Kincl; Roman Panovský; Martin Pešl; Jan Máchal; Lenka Juříková; Jana Haberlová; Lucia Masárová Journal: Sci Rep Date: 2020-11-27 Impact factor: 4.379