• genotype-phenotype correlations
• muscle magnetic resonance imaging
• neuromuscular disorders

This doctoral thesis has a wide scope, resulting from a research effort made in three directions: i) to better characterize genotype-phenotype correlations in different forms of neuromuscular disorders; ii) to highlight the usefulness of muscle MRI in differential diagnosis and iii) to expand its use to improve definition of pathogenic mechanisms in muscular pathologies.
This dissertation initially describes present knowledge of several diseases discussed in my research thesis. The state of the art of muscle MRI, a non invasive diagnostic tool useful in directing genetic tests and achieving a correct diagnosis, is highlighted in a separate chapter being the “hot topic” of my work.
In the section regarding the clinical and genetics studies, I also reported the efforts spent for characterizing new forms of muscle diseases and better genotype-phenotype correlations: the chapter mainly describes two new forms of distal SMA, a presintomatic form of lipidic myopathy and the genetic breakdown in several genes related to congenital muscular dystrophy.
This contribution is relevant to gain new knowledge in neurogenic and myopathyc clinical conditions and to describe the relative frequency of CMD subtypes and the mutation's incidence among different CMD genes.
In the other section regarding muscle MRI studies, I discuss data onto whether muscle myoimaging could be a helpful tool in both diagnosis and prognosis in TRPV4-related disorders. More specifically, this part of the thesis presents data for an improved definition of the pattern of muscle involvement in TRPV4-pathies and demonstrate that muscle MRI is useful in the early differentiation between forms of distal SMA and Charcot-Marie-Tooth. This part also argues how muscle MRI can be used to drive molecular studies in congenital myopathies with the description of the clinical case of two sisters in whom clinical and immunoistological findings were misleading.
In a separate chapter, my research thesis also highlight the sensitivity and specificity of the visual analysis of muscle MRI to identify inner muscle alterations able to differentiate neurogenic diseases involving distal muscles from the forms with primary muscular involvement. The pattern of involvement within muscles, that is not something normally captured by standardized “Mercuri grading” approach seems to be a useful diagnostic marker of late neurogenic changes.
In addition, putting together my neurology experience with my neuropsychiatric competence in a multidisciplinary work with language therapist and psychologist, a special clinical work possible at IRCCS Stella Maris, I discuss in the last part of the thesis the presence and characteristics of literacy deficits in DMD children and analyse the neuropsychological profiles associated with reading abilities when compared to similarly aged dyslexic children. This study shows how a multi-component cognitive deficit may contribute to specific literacy difficulties in DMD with rapid access to lexicon and phonological processing. Early recognition of deficits might help DMD toddlers prior to entering primary school prompting appropriate rehabilitation of reading disabilities.