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Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome).

  • Micalizzi A CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Poretti A Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
  • Romani M CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Ginevrino M CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Mazza T CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Aiello C Laboratory of Molecular Medicine, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Zanni G Laboratory of Molecular Medicine, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Baumgartner B Pediatric Neurology, Children's Hospital, Landshut, Germany.
  • Borgatti R Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute IRCCS Eugenio Medea, Lecco, Italy.
  • Brockmann K Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University of Goettingen, Goettingen, Germany.
  • Camacho A Section of Pediatric Neurology, Hospital Universitario 12 de Octubre, Department of Medicine, Universidad Complutense, Madrid, Spain.
  • Cantalupo G Child Neuropsychiatry, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy.
  • Haeusler M Department of Pediatrics, Division of Neuropediatrics and Social Pediatrics, University Hospital, RWTH Aachen, Aachen, Germany.
  • Hikel C Social Pediatic Centrum (SPZ), St Vinzenz Hospital, Dinslaken, Germany.
  • Klein A Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
  • Mandrile G SCDU Medical Genetics, Hospital Città della Salute e della Scienza di Torino, Turin, Italy.
  • Mercuri E Paediatric Neurology Unit, Catholic University, Rome, Italy.
  • Rating D Pediatrics, St Marien and St Anna Hospital, Ludwigshafen, Germany.
  • Romaniello R Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute IRCCS Eugenio Medea, Lecco, Italy.
  • Santorelli FM Molecular Medicine, IRCCS Stella Maris, Pisa, Italy.
  • Schimmel M Division of Pediatric Neurology, Children's Hospital, Klinikum Augsburg, Augsburg, Germany.
  • Spaccini L Clinical Genetic Unit, Department of Women, Mother and Neonates, 'Vittore Buzzi' Children Hospital, Istituti Clinici di Perfezionamento, Milan, Italy.
  • Teber S Department of Pediatric Neurology, Ankara Pediatrics, Hematology-Oncology Training and Research Hospital, Ankara, Turkey.
  • von Moers A Department of Pediatrics, DRK Kliniken Berlin Westend, Berlin, Germany.
  • Wente S Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Department of Pediatrics and Adolescent Medicine, University of Goettingen, Goettingen, Germany.
  • Ziegler A Division of Pediatric Neurology, University Children's Hospital Heidelberg, Germany.
  • Zonta A SCDU Medical Genetics, Hospital Città della Salute e della Scienza di Torino, Turin, Italy.
  • Bertini E Laboratory of Molecular Medicine, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • Boltshauser E Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland.
  • Valente EM CSS-Mendel Institute, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
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  • 2016-03-03
Published in:
  • European journal of human genetics : EJHG. - 2016
Adolescent
Cerebellar Ataxia
Cerebellum
Child
Child, Preschool
Cysts
Eye Diseases
Female
Founder Effect
Frameshift Mutation
Haplotypes
Humans
Infant
Intellectual Disability
Laminin
Male
Pedigree
Syndrome
English Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti-Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS. Here we report the detailed clinical, neuroimaging and genetic characterization of 18 PBS patients from 15 unrelated families. Biallelic LAMA1 variants were identified in 14 families (93%). The only non-mutated proband presented atypical clinical and neuroimaging features, challenging the diagnosis of PBS. Sixteen distinct variants were identified, which were all novel. In particular, the frameshift variant c.[2935delA] recurred in six unrelated families on a shared haplotype, suggesting a founder effect. No LAMA1 variants could be detected in 27 probands with different cerebellar dysplasias or non-progressive cerebellar ataxia, confirming the strong correlate between LAMA1 variants and PBS.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/263403
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