Encephalopathies with intracranial calcification in children: Clinical and genetic characterization

Davide Tonduti, Celeste Panteghini, Anna Pichiecchio, Alice Decio, Miryam Carecchio, Chiara Reale, Isabella Moroni, Nardo Nardocci, Jaume Campistol, Angela Garcia-Cazorla, Belen Perez Duenas, Giovanna Zorzi, Anna Ardissone, Tiziana Granata, Elena Freri, Federica Zibordi, Francesca Ragona, Stefano D'Arrigo, Veronica Saletti, Silvia EspositoChiara Pantaleoni, Daria Riva, Valentina De Giorgis, Cristina Cereda, Maria Luisa Valente, Daisy Sproviero, Maria Pilar Poo Arguelles, Carmen Fons Estupina, Anna Maria Sans Fito, Loreto Martorell Sampol, Maria Del Mar O'Callaghan Gordo, Carlos Ignacio Ortez Gonzalez, Veronica Gonzalez Alvarez, Nuria Garcia-Segarra, Carlo Fusco, Enrico Bertini, Daria Diodato, Elisa Fazzi, Jessica Galli, Luisa Chiapparini, Barbara Garavaglia, Simona Orcesi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number135
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - Aug 16 2018


  • Aicardi-Goutières syndrome
  • Cerebral calcification
  • Leukodystrophy
  • Next generation sequencing

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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