Neuropediatrics 2013; 44 - FV13_06
DOI: 10.1055/s-0033-1337728

Ataxia, cognitive impairment, and ocular motor apraxia with cerebellar cysts and dysplasia: A new form of dystroglycanopathy?

A Poretti 1, M Häusler 2, A van Moers 3, B Baumgartner 4, K Zerres 5, A Klein 6, C Aiello 7, G Zanni 7, FM Santorelli 8, TAGM Huisman 1, EM Valente 9, J Weis 10, E Bertini 7, E Boltshauser 6
  • 1The Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology, Baltimore, Maryland, United States
  • 2Pädiatrische Klinik, RWTH Universitätsspital, Aachen, Germany
  • 3Pädiatrische Klinik, DRK Kliniken Berlin West, Berlin, Germany
  • 4Neuropädiatrie, Kinderspital, Landshut, Germany
  • 5Institut für Humangenetik der RWTH, Aachen, Germany
  • 6Neuropädiatrische Abteilung, Universitäts-Kinderklinik, Zürich, Switzerland
  • 7Laboratory of Molecular Medicine, Bambino Gesù Children's Research Hospital, Rome, Italy
  • 8Stella Maris Institute, IRCCS Casa Sollievo della Sofferenza Institute, Calambrone, Italy
  • 9Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, Roma, Italy
  • 10Institut für Neuropathologie, Universitätsklinikum der RWTH, Aachen, Germany

Aims: Cerebellar cysts are a rare finding in pediatric neuroimaging and are rather characteristic for some congenital muscular dystrophies (CMD) due to impaired glycosylation of α-dystroglycan. We aim to evaluate the MRI spectrum, characterize neurological/ophthalmological features and cognitive outcome, and report genetic analysis in seven children (including three siblings) with an apparently new syndrome characterized by cerebellar cysts.

Methods: All images were qualitatively evaluated for infra- and supratentorial abnormalities. Data about neurological/ophthalmological features and outcome were collected from clinical history and follow-up examination. POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, and GPR56 genes were screened in all patients. In three children, a SNP 6.0-Array was also performed.

Results: The seven patients were four males and three females. At a mean age of 7.2 years (range 3.5 to 13.5 years), cognitive impairment and ataxia were found in all patients, ocular motor apraxia in six, and severe myopia in three. Qualitative MR evaluation showed cerebellar cysts in the cerebellar hemispheres and vermis in all patients. Additional MR findings included cerebellar dysplasia and an enlarged fourth ventricle in all children, vermian hypoplasia and brain stem morphological abnormalities in six, and an elongated and squared shape of the fourth ventricle in five. In all patients, no mutations were found in the POMT1, POMT2, POMGnT1, FKRP, FKTN, LARGE, and GPR56 genes. The SNP array showed no pathogenetic imbalances in all children evaluated.

Conclusion: The seven children share the same clinical and neuroimaging phenotype including cognitive impairment, ataxia, ocular motor apraxia, cerebellar cysts, and cerebellar dysplasia. These are features of dystroglycanopathies. However, weakness, a key feature of CMD, was not a finding. In addition, no mutations were found within the known dystroglycanopathy genes. Therefore, we suggest that the reported clinical and neuroimaging phenotype may represent a new syndrome related to the glycosylation defect spectrum.