Journal of Clinical Medicine (May 2021)
Movement Disorders in Children with a Mitochondrial Disease: A Cross-Sectional Survey from the Nationwide Italian Collaborative Network of Mitochondrial Diseases
- Chiara Ticci,
- Daniele Orsucci,
- Anna Ardissone,
- Luca Bello,
- Enrico Bertini,
- Irene Bonato,
- Claudio Bruno,
- Valerio Carelli,
- Daria Diodato,
- Stefano Doccini,
- Maria Alice Donati,
- Claudia Dosi,
- Massimiliano Filosto,
- Chiara Fiorillo,
- Chiara La Morgia,
- Costanza Lamperti,
- Silvia Marchet,
- Diego Martinelli,
- Carlo Minetti,
- Maurizio Moggio,
- Tiziana Enrica Mongini,
- Vincenzo Montano,
- Isabella Moroni,
- Olimpia Musumeci,
- Elia Pancheri,
- Elena Pegoraro,
- Guido Primiano,
- Elena Procopio,
- Anna Rubegni,
- Roberta Scalise,
- Monica Sciacco,
- Serenella Servidei,
- Gabriele Siciliano,
- Costanza Simoncini,
- Deborah Tolomeo,
- Paola Tonin,
- Antonio Toscano,
- Flavia Tubili,
- Michelangelo Mancuso,
- Roberta Battini,
- Filippo Maria Santorelli
Affiliations
- Chiara Ticci
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Daniele Orsucci
- Unit of Neurology, San Luca Hospital, 55100 Lucca, Italy
- Anna Ardissone
- Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
- Luca Bello
- Neuromuscular Unit, Department of Neuroscience, University of Padova, 35121 Padua, Italy
- Enrico Bertini
- Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy
- Irene Bonato
- Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
- Claudio Bruno
- Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
- Valerio Carelli
- Programma di Neurogenetica, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy
- Daria Diodato
- Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy
- Stefano Doccini
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Maria Alice Donati
- A. Meyer Children Hospital, 50139 Florence, Italy
- Claudia Dosi
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Massimiliano Filosto
- Department of Clinical and Experimental Sciences, University of Brescia, NeMO-Brescia Clinical Center for Neuromuscular Diseases, 25064 Brescia, Italy
- Chiara Fiorillo
- Neuromuscular Disorders Unit, IRCCS Istituto Giannina Gaslini, DINOGMI, University of Genoa, 16147 Genoa, Italy
- Chiara La Morgia
- Programma di Neurogenetica, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy
- Costanza Lamperti
- Genetics and Neurogetics, Fondazione IRCCS Istituto Neurologico C. Besta, 20133 Milan, Italy
- Silvia Marchet
- Genetics and Neurogetics, Fondazione IRCCS Istituto Neurologico C. Besta, 20133 Milan, Italy
- Diego Martinelli
- Bambino Gesù Children’s Hospital IRCCS, 00165 Rome, Italy
- Carlo Minetti
- Neuromuscular Disorders Unit, IRCCS Istituto Giannina Gaslini, DINOGMI, University of Genoa, 16147 Genoa, Italy
- Maurizio Moggio
- Neuromuscular and Rare Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre University of Milan, 20122 Milan, Italy
- Tiziana Enrica Mongini
- Neuromuscular Unit, Department of Neuroscience “Rita Levi Montalcini”, University of Torino, 10124 Torino, Italy
- Vincenzo Montano
- Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy
- Isabella Moroni
- Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy
- Olimpia Musumeci
- Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
- Elia Pancheri
- Neurological Clinic, University of Verona, 37134 Verona, Italy
- Elena Pegoraro
- Neuromuscular Unit, Department of Neuroscience, University of Padova, 35121 Padua, Italy
- Guido Primiano
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Elena Procopio
- A. Meyer Children Hospital, 50139 Florence, Italy
- Anna Rubegni
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Roberta Scalise
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Monica Sciacco
- Neuromuscular and Rare Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre University of Milan, 20122 Milan, Italy
- Serenella Servidei
- Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
- Gabriele Siciliano
- Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy
- Costanza Simoncini
- Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy
- Deborah Tolomeo
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Paola Tonin
- Neurological Clinic, University of Verona, 37134 Verona, Italy
- Antonio Toscano
- Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
- Flavia Tubili
- A. Meyer Children Hospital, 50139 Florence, Italy
- Michelangelo Mancuso
- Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, 56126 Pisa, Italy
- Roberta Battini
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- Filippo Maria Santorelli
- IRCCS Fondazione Stella Maris, 56018 Pisa, Italy
- DOI
- https://doi.org/10.3390/jcm10102063
- Journal volume & issue
-
Vol. 10,
no. 10
p. 2063
Abstract
Movement disorders are increasingly being recognized as a manifestation of childhood-onset mitochondrial diseases (MDs). However, the spectrum and characteristics of these conditions have not been studied in detail in the context of a well-defined cohort of patients. We retrospectively explored a cohort of individuals with childhood-onset MDs querying the Nationwide Italian Collaborative Network of Mitochondrial Diseases database. Using a customized online questionnaire, we attempted to collect data from the subgroup of patients with movement disorders. Complete information was available for 102 patients. Movement disorder was the presenting feature of MD in 45 individuals, with a mean age at onset of 11 years. Ataxia was the most common movement disorder at onset, followed by dystonia, tremor, hypokinetic disorders, chorea, and myoclonus. During the disease course, most patients (67.7%) encountered a worsening of their movement disorder. Basal ganglia involvement, cerebral white matter changes, and cerebellar atrophy were the most commonly associated neuroradiological patterns. Forty-one patients harbored point mutations in the mitochondrial DNA, 10 carried mitochondrial DNA rearrangements, and 41 cases presented mutations in nuclear-DNA-encoded genes, the latter being associated with an earlier onset and a higher impairment in activities of daily living. Among our patients, 32 individuals received pharmacological treatment; clonazepam and oral baclofen were the most commonly used drugs, whereas levodopa and intrathecal baclofen administration were the most effective. A better delineation of the movement disorders phenotypes starting in childhood may improve our diagnostic workup in MDs, fine tuning management, and treatment of affected patients.
Keywords