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The phenotype and genotype of congenital myopathies based on a large pediatric cohort
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  • Daniel Natera-de Benito,
  • Carlos Ortez,
  • Cristina Jou,
  • Cecilia Jiménez-Mallebrera,
  • Anna Codina,
  • Laura Carrera-García,
  • Jesica Exposito-Escudero,
  • Sergi Cesar,
  • Loreto Martorell,
  • PIA GALLANO,
  • Lidia González-Quereda,
  • Daniel Cuadras,
  • Jaume Colomer,
  • Delia Yubero,
  • Francesc Palau,
  • Andrés Nascimento
Daniel Natera-de Benito
Hospital Sant Joan de Déu
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Carlos Ortez
Hospital Sant Joan de Deu
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Cristina Jou
Hospital Sant Joan de Deu
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Cecilia Jiménez-Mallebrera
Hospital Sant Joan de Déu
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Anna Codina
Hospital Sant Joan de Deu
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Laura Carrera-García
Sant Joan de Deu Hospital
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Jesica Exposito-Escudero
Hospital Sant Joan de Deu
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Sergi Cesar
Hospital Sant Joan de Deu
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Loreto Martorell
Hospital Sant Joan de Déu, University of Barcelona
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PIA GALLANO
, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB)
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Lidia González-Quereda
Hospital de la Santa Creu i Sant Pau
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Daniel Cuadras
Hospital Sant Joan de Deu
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Jaume Colomer
Hospital Sant Joan de Deu
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Delia Yubero
Hospital Sant Joan de Deu
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Francesc Palau
Hospital Sant Joan de Deu
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Andrés Nascimento
Neuromuscular Unit, Department of Paediatric Neurology, Hospital Sant Joan de Déu
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Abstract

We report the clinical, histopathological and molecular characterization of 104 patients with congenital myopathy (CM) managed at a single center. The most common histopathological subtype was core myopathy (42%). Patients with severe endomysial fibrosis were more commonly unable to walk than patients with only a mild grade (56% vs 16%). Inability to walk was also more prevalent in patients with severe fatty replacement (44% vs 19%). The genetic etiology was more frequently identified among those patients with “specific” histologic findings (74% vs 62%). A definite molecular diagnosis was reached in 65/104 patients (62%), with RYR1 (24/104) and TTN (8/104) as the most frequent causative genes. Neonatal onset occurred in 56%. Independent ambulation was achieved by 74%. Patients who walked late were more likely to become wheelchair-dependent. Respiratory support was needed in 1/3 patients. Gastrostomy placement was required in 15%. Cardiac involvement was observed in 3%, scoliosis in 43%, and intellectual disability in 6%. This study provides an updated picture of the clinical, histopathological and molecular landscape of CMs. Independently of the causative gene, fibrosis and fatty replacement in muscle biopsy is significantly associated with clinical severity. Mutations in TTN are responsible for a higher proportion of cases than previously thought.