title: MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients.
abstract: Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions.
  
  
  
  As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps.
  
  
  
  This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder.
authors.affiliation: IRCCS Stella Maris, Molecular Medicine and Neuromuscular Disorders, Via dei Giacinti 2, 56128, Calambrone, Pisa, Italy. chi.fiorillo@gmail.com.|Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternad and Child Health, University of Genova, University of Genoa, Genoa, Italy. chi.fiorillo@gmail.com.
authors.forename: C
authors.initials: C
authors.lastname: Fiorillo
authors.affiliation: IRCCS Stella Maris, Molecular Medicine and Neuromuscular Disorders, Via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Astrea
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Savarese
authors.affiliation: IRCCS Stella Maris, Molecular Medicine and Neuromuscular Disorders, Via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.affiliation: Unit of Pediatric Neurology and Muscular Disorders, Istituto G.Gaslini, Genoa, Italy.|Department of Neuroscience, Center of Myology and Neurodegenerative Disorders, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Brisca
authors.affiliation: Unit of Pediatric Neurology and Muscular Disorders, Istituto G.Gaslini, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Trucco
authors.affiliation: Unit of Pediatric Neurology and Muscular Disorders, Istituto G.Gaslini, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pedemonte
authors.affiliation: IRCCS Stella Maris, Molecular Medicine and Neuromuscular Disorders, Via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Trovato
authors.affiliation: Department of Neurosciences and Reproductive and Odontostomatologic Sciences, University Federico II, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ruggiero
authors.affiliation: Department of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Vercelli
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Don Carlo Gnocchi ONLUS Foundation, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tasca
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pane
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fanin
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bello
authors.affiliation: Unit of Pediatric Neurology and Muscular Disorders, Istituto G.Gaslini, Genoa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Broda
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Musumeci
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rodolico
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Messina
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: G L
authors.initials: GL
authors.lastname: Vita
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sframeli
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Foundation C Besta Neurological Institute, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gibertini
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Foundation C Besta Neurological Institute, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Foundation C Besta Neurological Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.affiliation: Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Foundation C Besta Neurological Institute, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Maggi
authors.affiliation: Center for Neuromuscular and Neurological Rare Diseases, S. Camillo-Forlanini Hospital, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Petrucci
authors.affiliation: Department of Systems Medicine (Neurology), University of Tor Vergata, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Massa
authors.affiliation: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternad and Child Health, University of Genova, University of Genoa, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Grandis
authors.affiliation: Department of Clinical and Experimental Medicine and Nemo Sud Clinical Centre, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pegoraro
authors.affiliation: Department of Paediatric Neurology, Catholic University, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Department of Neurosciences "Rita Levi Montalcini", University of Turin, Turin, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Mongini
authors.affiliation: Department of Neurosciences and Reproductive and Odontostomatologic Sciences, University Federico II, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Nigro
authors.affiliation: Unit of Pediatric Neurology and Muscular Disorders, Istituto G.Gaslini, Genoa, Italy.|Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternad and Child Health, University of Genova, University of Genoa, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Minetti
authors.affiliation: IRCCS Stella Maris, Molecular Medicine and Neuromuscular Disorders, Via dei Giacinti 2, 56128, Calambrone, Pisa, Italy.
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.affiliation: Department of Neuroscience, Center of Myology and Neurodegenerative Disorders, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bruno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D035002:Lower Extremity / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000175:diagnosis* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains
keywords: Distal myopathy; Muscle MRI; Muscle biopsy; Myosin heavy chain; Whole exome sequencing