Giulia Iapadre1, Giovanni Morana2, Maria Stella Vari3, Francesca Pinto3, Paola Lanteri4, Alessandra Tessa5, Filippo Maria Santorelli6, Pasquale Striano3, Alberto Verrotti7. 1. Department of Pediatrics, University of L'Aquila, L'Aquila, Italy. 2. Neuroradiology, Department of Head and Neck, "G. Gaslini" Institute, Genova, Italy. 3. Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genova, Italy. 4. Child Neuropsychiatry, Department of Head and Neck, "G. Gaslini" Institute, Genova, Italy. 5. Molecular Medicine and Neurogenetics, IRCCS Stella Maris, Pisa, Italy. 6. Child Neurology, IRCCS Stella Maris, Pisa, Italy. 7. Department of Pediatrics, University of L'Aquila, L'Aquila, Italy. Electronic address: alberto.verrottidipianella@univaq.it.
Abstract
BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported. RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype. CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.
BACKGROUND:Charcot-Marie-Tooth (CMT) neuropathies represent the most common forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about one third of all CMT cases. Variants in the MFN2 gene have been recognized to be a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2 have been identified, leading to different neurological clinical spectrum, varying from hereditary neuropathies to more severe clinical phenotypes. Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few sporadic or familial cases, homozygous or compound heterozygous mutations have been reported. RESULTS: We describe a child carrying a novel homozygous MFN2 mutation leading to an early-onset sensorimotor axonal neuropathy with an atypical and severe phenotype. CONCLUSION: The case highlights a very rare mechanism of inheritance for MFN2 mutations and expands the clinical and allelic variance of severe CMT2A phenotype. Moreover, it proposes the involvement of cerebellar peduncles observed at neuroimaging as a novel clue to suspect the diagnosis and address genetic testing.
Authors: Silvana Guerriero; Francesco D'Oria; Giacomo Rossetti; Rosa Anna Favale; Stefano Zoccolella; Giovanni Alessio; Vittoria Petruzzella Journal: Int Med Case Rep J Date: 2020-02-20
Authors: Delfina Larrea; Marta Pera; Adriano Gonnelli; Rubén Quintana-Cabrera; H Orhan Akman; Cristina Guardia-Laguarta; Kevin R Velasco; Estela Area-Gomez; Federica Dal Bello; Diego De Stefani; Rita Horvath; Michael E Shy; Eric A Schon; Marta Giacomello Journal: Hum Mol Genet Date: 2019-06-01 Impact factor: 6.150