Evidence-Based Consensus and Systematic Review on Reducing the Time to Diagnosis of Duchenne Muscular Dystrophy

Abstract

Section 1: Reducing the time to diagnosis of DMD Statement 1: The following signs, symptoms, and characteristics should be considered typical indicators of DMD: calf hypertrophy (pseudohypertrophy); delayed walking; difficulty climbing/descending stairs; difficulty rising from the floor; difficulty running/walking; elevated serum CK levels (including elevated ALT and AST); a family history of DMD; frequent falls; Gowers' sign; male sex; and muscle weakness. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CGH, comparative genome hybridization; CK, creatine kinase; DMD, Duchenne muscular dystrophy; GRADE, Grading of Recommendations Assessment, Development, and Evaluation. *The level of evidence for most of the statements was graded as either low or moderate, owing to the fact that most of the studies included here are observational in nature rather than randomized controlled trials (due to the nature of this initiative). When there were multiple corroborative supporting observational studies, we have selected "moderate" for quality of evidence. †Consensus: A + = strongly agree; A = agree; N = neither agree nor disagree; D = disagree; D + = strongly disagree. Grade of recommendation: 1A = strong recommendation, high-quality evidence; 1B = strong recommendation, moderate-quality evidence; 1C = strong recommendation, low-quality or very low-quality evidence; 2A = weak recommendation, high-quality evidence; 2B = weak recommendation, moderate-quality evidence; 2C = weak recommendation, low-quality or very low-quality evidence. ‡Where applicable depending on country-specific legislation on presymptomatic testing of patients aged ≤18 years.

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

“…19 Because of the enormous size of the dystrophin gene, the mutational spectrum is tremendously heterogeneous, and the genetic diagnostic approach must be both accurate and sensitive. 20 Because these are estimated to be less than 1% in various patient series, 21,22,23,24 their impact on the detection rate should be low, and only a few cases might have been missed. Ethnicity may also play a role in mutation type frequency, as already described 23 ; only the adoption of a single and fully accurate method able to detect all mutation types, such as whole-genome sequencing (WGS), will allow us to unravel these events and their frequency in the various populations.…”

Is it the right time for an infant screening for Duchenne muscular dystrophy?

“…The reason for 47% answering “not sure” was mainly related to the absence of available treatments for patients younger than 5 years of age (at the time of investigation ataluren has not been yet approved for children as young as 2 years). Moreover, 75% believed that CK-based NBS would improve standards of care and family planning [ 41 ]. NBS has been discussed for many years, but now, with promising treatments already available or on the horizon, it became an even more appropriate matter.…”

Consenso colombiano para el seguimiento de pacientes con Distrofia muscular de Duchenne

“…La sospecha diagnóstica de la DMD se debe considerar en un niño con cualquiera de los siguientes hallazgos: debilidad proximal a partir de los dos a cinco años; retraso en el desarrollo psicomotor; dificultad para subir o bajar escaleras; caídas frecuentes; dificultad para levantarse del suelo (signo de Gowers) y anomalía de la marcha (marcha en punta de pies); hipertrofia (pseudohipertrofia) de la pantorrilla, en presencia o no de antecedente familiar similar, sumado a aumento marcado de creatina quinasa (CK) en suero, 50-100 veces más alta del límite normal superior de niños pequeños no afectados (26) y ocasionalmente niveles elevados de transaminasas séricas (aspartato y alanina aminotransferasas, también producidas por células musculares) (27).…”