Encephalopathies with intracranial calcification in children: clinical and genetic characterization
Por:
Tonduti D, Panteghini C, Pichiecchio A, Decio A, Carecchio M, Reale C, Moroni I, Nardocci N, Campistol-Plana J, Garcia-Cazorla A, Pérez-Dueñas B, Cerebral Calcification International Study Group, Chiapparini L, Garavaglia B and Orcesi S
Publicada:
16 ago 2018
Ahead of Print:
16 ago 2018
Resumen:
Background: We present a group of patients affected by a paediatric onset genetic encephalopathy with cerebral calcification of unknown aetiology studied with Next Generation Sequencing (NGS) genetic analyses.
Methods: We collected all clinical and radiological data. DNA samples were tested by means of a customized gene panel including fifty-nine genes associated with known genetic diseases with cerebral calcification.
Results: We collected a series of fifty patients. All patients displayed complex and heterogeneous phenotypes mostly including developmental delay and pyramidal signs and less frequently movement disorder and epilepsy. Signs of cerebellar and peripheral nervous system involvement were occasionally present. The most frequent MRI abnormality, beside calcification, was the presence of white matter alterations; calcification was localized in basal ganglia and cerebral white matter in the majority of cases. Sixteen out of fifty patients tested positive for mutations in one of the fifty-nine genes analyzed. In fourteen cases the analyses led to a definite genetic diagnosis while results were controversial in the remaining two.
Conclusions: Genetic encephalopathies with cerebral calcification are usually associated to complex phenotypes. In our series, a molecular diagnosis was achieved in 32% of cases, suggesting that the molecular bases of a large number of disorders are still to be elucidated. Our results confirm that cerebral calcification is a good criterion to collect homogeneous groups of patients to be studied by exome or whole genome sequencing; only a very close collaboration between clinicians, neuroradiologists and geneticists can provide better results from these new generation molecular techniques.
Filiaciones:
Tonduti D:
Child Neurology Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy.
Child Neurology Unit, V. Buzzi Children's Hospital, Milan, Italy.
Panteghini C:
Molecular Neurogenetics Unit, Movement Disorders Diagnostic Section, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Pichiecchio A:
Department of Neuroradiology, IRCCS Mondino Foundation, Pavia, Italy
Decio A:
Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy
Neuropsychiatry and Neurorehabilitation Unit, IRCCS Medea, Bosisio Parini Lecco, Italy
Carecchio M:
Child Neurology Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Molecular Neurogenetics Unit, Movement Disorders Diagnostic Section, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Department of Medicine and Surgery, PhD Programme in Molecular and Translational Medicine, University of Milan Bicocca, Monza, Italy
Reale C:
Molecular Neurogenetics Unit, Movement Disorders Diagnostic Section, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Moroni I:
Child Neurology Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Nardocci N:
Child Neurology Unit, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Campistol-Plana J:
Department of Child Neurology, Pediatric Research Institute, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Garcia-Cazorla A:
Department of Child Neurology, Pediatric Research Institute, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Pérez-Dueñas B:
Department of Child Neurology, Pediatric Research Institute, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
Chiapparini L:
Department of Neuroradiology, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Garavaglia B:
Molecular Neurogenetics Unit, Movement Disorders Diagnostic Section, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
Orcesi S:
Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy
gold, Green Published
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