Qualitative and quantitative muscle ultrasound in patients with Duchenne muscular dystrophy: Where do sonographic changes begin?

Objective: The number of studies investigating and understanding the disease mechanisms of Duchenne muscular dystrophy (DMD) in human clinical trials have increased substantially over the last decade. Suitable clinical instruments for the measurement of disease progress and drug efficiency are mandatory, but currently not available, especially in the youngest patients. The aim of this study was to detect a reproducible pattern of muscle involvement in early stages potentially preceding evidence of motor regression. Material and methods: A cohort of 25 DMD patients aged 1-6 years at the first presentation were examined at multiple timepoints and compared with age-matched healthy controls. Muscle ultrasound was quantified using computer-analyzed gray scale levels (GSL) and blinded visual rating, using a modified Heckmatt scale. Results: Changes in muscle echogenicity in DMD patients occurred very early, clearly preceding motor regression and in some cases, even before the motor plateau phase was reached. Visual rating and GSL identified the earliest changes in the proximal adductor magnus muscle. Conclusion: Muscle ultrasound can be used as an additional method to assess the disease progression and for decision-making in paucisymptomatic DMD patients. Sonographic changes in the ad-ductor magnus muscle seem to be the first detectable changes with a recognisable pattern. (c) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved

Correction to: De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy.

Unfortunately, in the first sentence in the abstract, a spelling mistake was introduced during the production process after our proofreading. The wording was changed from “aims” to “aimsed.” Heather M. McLaughlin was not listed among the authors. The original article has been corrected

De novo variants in <em>SNAP25</em> cause an early-onset developmental and epileptic encephalopathy.

Purpose: This study aimsed to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. Methods: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed. Results: The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex. Conclusion: We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed “SNAREopathies.”