COL4A1 Mutations Associated with a Characteristic Pattern of Intracranial Calcification

J. Livingston; D. Doherty; S. Orcesi; D. Tonduti; A. Piechiecchio; R. La Piana; E. Tournier-Lasserve; A. Majumdar; S. Tomkins; G. Rice; R. Kneen; M. van der Knaap; Y. Crow

doi:10.1055/s-0031-1295493

Neuropediatrics, Table of Contents

Neuropediatrics 2011; 42(06): 227-233
DOI: 10.1055/s-0031-1295493

Original Article

COL4A1 Mutations Associated with a Characteristic Pattern of Intracranial Calcification

J. Livingston

¹Department of Paediatric Neurology, Leeds General Infirmary, Leeds, UK

,

D. Doherty

²Divisions of Developmental Medicine and Genetic Medicine, University of Washington Seattle Childrens Hospital, Seattle, Washington, USA

,

S. Orcesi

³Unit of Child Neurology and Psychiatry, IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy

,

D. Tonduti

³Unit of Child Neurology and Psychiatry, IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy

,

A. Piechiecchio

³Unit of Child Neurology and Psychiatry, IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy

,

R. La Piana

⁴Department of Neuroradiology, Montreal Neurological Institute, Montreal, CanadaM

,

E. Tournier-Lasserve

⁵Laboratoire de Genetique, Groupe Hospatilier Lariboisiere-Fernand-Widal, Paris, France

,

A. Majumdar

⁶Department of Paediatric Neurology, Bristol Children’s Hospital, Bristol, UK

,

S. Tomkins

⁷Department of Clinical Genetics, Bristol, UK

,

G. Rice

⁸Department of Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester Foundation Trust University Hospitals, University of Manchester, Manchester, UK

,

R. Kneen

⁹Neuroscience Unit, Alder Hey Childrens NHS Foundation Trust, Littlewood, Liverpool, UK

,

M. van der Knaap

¹⁰Department of Child Neurology VU University Medical Center, Amsterdam, The Netherlands

,

Y. Crow

¹¹Department of Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK

› Author Affiliations

Abstract

Introduction:

Intracranial calcification (ICC) is a relatively common radiological finding in children undergoing investigation for neurological disorders. Many causes are recognised, and ICC is often regarded as a non-specific sign.

Methods:

From an ongoing study of ICC, we identified 5 patients with characteristic radiological features, in whom a mutation in the COL4A1 gene was found.

Results:

All patients had CT and MR imaging. MR images demonstrated features of periventricular leukomalacia with irregular dilatation of the lateral ventricles with or without porencephaly, loss of hemispheric white matter volume, and high signal on T₂ and FLAIR sequences within periventricular and deep white matter. Calcification was apparent on MR in 4 patients. CT scans demonstrated spot and linear calcification in the subependymal region and around areas of porencephaly. Calcification was also visible in the deep cerebral white matter and basal ganglia. 1 patient showed calcification in the central pons.

Conclusion:

ICC occurs in COL4A1-related disease. The radiological features are distinct from other conditions demonstrating recognisable patterns of ICC, such as congenital cytomegalovirus infection and Aicardi-Goutiéres syndrome. In the absence of a known risk factor for periventricular leukomalacia, the presence of these radiological findings should suggest the possibility of COL4A1-related disease.

Key words

intracranial calcification - COL4A1 - periventricular leukomalacia

Full Text

References

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