Search

Assessing myocardial strain remains challenging, particularly in the pediatric population, due to the smaller heart sizes, higher heart rates, and variability in strain parameters compared to adult populations. This study aimed to investigate the utility of myocardial strain measurements using cardiac magnetic resonance-feature tracking (CMR-FT) for early diagnosis of Duchenne muscular dystrophy (DMD) in pediatric patients. Twenty-eight DMD patients and 20 healthy controls were involved in this study. Global circumferential, longitudinal, and radial strain (GCS, GLS, and GRS) were measured for the left ventricle (LV) using CMR-FT. Segmental strain values only of the inferolateral and anterolateral LV segments in DMD patients without late gadolinium enhancement (LGE) and DMD patients with LGE were compared to the healthy controls. Strain measurements using CMR-FT in DMD patients were considerably lower than those of healthy controls, with all p-values lower than 0.001. DMD patients without LGE showed decreased inferolateral and anterolateral segmental values only relative to healthy controls. The same behavior was maintained for the LV geometry. Multivariable linear regression demonstrated that the end-systole (ES) wall thicknesses and thickening were associated with decreased GCS and GLS. CMR-FT is crucial in detecting cardiac abnormalities in patients with DMD. It represents an innovative imaging biomarker that can detect initial myocardial alterations in DMD cardiomyopathy without relying on gadolinium. [ABSTRACT FROM AUTHOR]

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9–50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN. [ABSTRACT FROM AUTHOR]

Byline: Malek. Mansour, Thouraya. Ben Younes, Wafa. Kacem, Ridha. Mrissa Sir, Neuromyelitis optica spectrum disorders (NMOSD) represent a severe inflammatory disease of the central nervous system (CNS) that predominantly affects [...]

Muscle diseases with prominent limb-joint contractures (LJCs) are a subgroup of rare neuromuscular disorders. Prominent LJCs are not specific to genetic myopathies. Myositis can also induce severe contractures, especially in the late stages. We report the case of a 12-year-old girl with a 3-year history of painful muscular weakness with generalized LJCs. The inflammatory pattern associated with positive anti-PM/Scl antibodies on muscle biopsy allowed us to initially retain the diagnosis of scleromyositis. After 12 months of corticosteroids and immunosuppressive treatment, there was no clinical improvement, and creatine kinase levels remained high (over 10 times the normal value). A second muscle biopsy showed persistent inflammatory infiltrate with the appearance of dystrophic features. Immunohistochemical analysis showed the absence of class 1 major histocompatibility complex expression on muscle fibres, raising the possibility of the diagnosis of muscular dystrophy. Whole-exome sequencing revealed a missense homozygous novel mutation c.386G>T (p. Arg129Ile) on the calpain 3 gene, finally confirming the diagnosis of autosomal recessive limb-girdle muscular dystrophy recessive type 1 (or calpainopathy). This case report highlights the diagnostic challenges and the importance of a comprehensive evaluation in cases of muscle diseases with prominent LJCs. [ABSTRACT FROM AUTHOR]

ATP1A3 mutations have now been recognized in infants, children, and adults presenting with a diverse group of neurological phenotypes, including rapid-onset dystonia-parkinsonism, alternating hemiplegia of childhood, and most recently, cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome. The phenotypic spectrum of ATP1A3 -related neurological disorders continues to expand. In this case study, we report on early life epilepsy with episodic apnea potentially secondary to ATP1A3 mutation in a Tunisian child., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)