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Eugenio Mercuri, MD; Haluk Topaloglu, MD; Martin Brockington, BSc; Angela Berardinelli, MD; Anna Pichiecchio, MD; Filippo Santorelli, MD; Mary Rutherford, MD; Beril Talim, MD; Enzo Ricci, MD; Thomas Voit, MD; Francesco Muntoni, MD

Arch Neurol. 2006;63:251-257.

Objectives  To report the spectrum of brain magnetic resonance imaging findings in 13 patients with congenital muscular dystrophy and FKRP gene mutations and to explore possible genotype-phenotype correlations.

Design  We retrospectively reviewed brain magnetic resonance imaging in patients with congenital muscular dystrophy and FKRP gene mutations.

Patients  Thirteen patients with congenital muscular dystrophy and mutations in the FKRP gene.

Results  Five of the 13 patients had the typical phenotype originally described for congenital muscular dystrophy (MDC1C) with normal intelligence and normal brain magnetic resonance imaging while 3 other patients had isolated cerebellar cysts and mental retardation without any other sign of posterior fossa of supratentorial abnormalities. In the remaining 5 patients cerebellar cysts were associated with structural brain changes involving the posterior fossa and the cortex, ranging from focal unilateral periventricular nodular heterotopia to marked cerebellar dysplasia and pontine hypoplasia. In 2 of these 5 patients the severity and distribution of changes resembled muscle-eye-brain disease in 1 patient who had mild Walker-Warburg syndrome. The distribution of FKRP gene mutations identified in this group of patients did not reveal any obvious association with the severity of central nervous system involvement.

Conclusions  The severity of central nervous system involvement observed in our patients in contrast broadly reflected the severity of the disruption of -dystroglycan glycosylation. In particular, dystroglycan expression was almost absent in the patients with muscle-eye-brain diseaselike phenotype and less severely reduced in the patients with congenital muscular dystrophy (MDC1C) with or without cerebellar cysts. This study further highlights the central role that dystroglycan has in neuronal migration.

Author Affiliations: Dubowitz Neuromuscular Centre, Department of Paediatrics (Drs Mercuri and Muntoni and Mr Brockington) and the Magnetic Resonance Imaging Unit (Dr Rutherford), Imperial College, Hammersmith Hospital Campus, London, United Kingdom; Institute of Neurology, Catholic University, Rome, Italy (Drs Mercuri and Ricci); Department of Child Neurology, Hacettepe Children's Hospital, Ankara, Turkey (Drs Topaloglu and Talim); Departments of Child Neurology (Dr Berardinelli) and Radiology (Dr Pichiecchio), Mondino Institute, Pavia, Italy; Molecular Medicine, Bambino Gesu, Rome (Dr Santorelli); and Department of Paediatrics and Paediatric Neurology, University Hospital of Essen, Germany (Dr Voit).

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