Encephalopathies with intracranial calcification in children: clinical and genetic characterization

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...

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Autores: Tonduti D, Panteghini C, Pichiecchio A, Decio A, Carecchio M, Reale C, Moroni I, Nardocci N, Campistol J, Garcia-Cazorla A, Perez Duenas B, Cerebral Calcification International Study Group, Chiapparini L, Garavaglia B, Orcesi S
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p14793
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14793
Access Level:acceso abierto
Palabra clave:Cerebral calcification
Leukodystrophy
Aicardi-Goutieres syndrome
Next generation sequencing
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spelling Encephalopathies with intracranial calcification in children: clinical and genetic characterizationTonduti DPanteghini CPichiecchio ADecio ACarecchio MReale CMoroni INardocci NCampistol JGarcia-Cazorla APerez Duenas BCerebral Calcification International Study GroupChiapparini LGaravaglia BOrcesi SCerebral calcificationLeukodystrophyAicardi-Goutieres syndromeNext generation sequencingBackground: 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.BMC2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14793Orphanet Journal of Rare DiseasesISSN: 17501172reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p147932026-05-27T12:37:41Z
dc.title.none.fl_str_mv Encephalopathies with intracranial calcification in children: clinical and genetic characterization
title Encephalopathies with intracranial calcification in children: clinical and genetic characterization
spellingShingle Encephalopathies with intracranial calcification in children: clinical and genetic characterization
Tonduti D
Cerebral calcification
Leukodystrophy
Aicardi-Goutieres syndrome
Next generation sequencing
title_short Encephalopathies with intracranial calcification in children: clinical and genetic characterization
title_full Encephalopathies with intracranial calcification in children: clinical and genetic characterization
title_fullStr Encephalopathies with intracranial calcification in children: clinical and genetic characterization
title_full_unstemmed Encephalopathies with intracranial calcification in children: clinical and genetic characterization
title_sort Encephalopathies with intracranial calcification in children: clinical and genetic characterization
dc.creator.none.fl_str_mv Tonduti D
Panteghini C
Pichiecchio A
Decio A
Carecchio M
Reale C
Moroni I
Nardocci N
Campistol J
Garcia-Cazorla A
Perez Duenas B
Cerebral Calcification International Study Group
Chiapparini L
Garavaglia B
Orcesi S
author Tonduti D
author_facet Tonduti D
Panteghini C
Pichiecchio A
Decio A
Carecchio M
Reale C
Moroni I
Nardocci N
Campistol J
Garcia-Cazorla A
Perez Duenas B
Cerebral Calcification International Study Group
Chiapparini L
Garavaglia B
Orcesi S
author_role author
author2 Panteghini C
Pichiecchio A
Decio A
Carecchio M
Reale C
Moroni I
Nardocci N
Campistol J
Garcia-Cazorla A
Perez Duenas B
Cerebral Calcification International Study Group
Chiapparini L
Garavaglia B
Orcesi S
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cerebral calcification
Leukodystrophy
Aicardi-Goutieres syndrome
Next generation sequencing
topic Cerebral calcification
Leukodystrophy
Aicardi-Goutieres syndrome
Next generation sequencing
description 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.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14793
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14793
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv Orphanet Journal of Rare Diseases
ISSN: 17501172
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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