Cortical heterotopia in LGMD2I

Abstract

A 40-year-old man, with a history of one generalized non-febrile seizure at the age of 4 years, presented with slowly progressive proximal muscle weakness in the four limbs since the age of 12 years and recent myalgia. Clinical examination confirmed that proximal symmetrical limb girdle weakness was predominant in the legs, together with bilateral moderate scapula alata and abdominal muscle weakness. Cognition was normal. CK level was 5400 U/l. Transthoracic echocardiography showed a slightly dilated cardiomyopathy. A vital capacity of 70% of the expected value was seen on respiratory function tests. Deltoid muscle biopsy showed slight dystrophic changes, and immunohistochemical analysis revealed reduced staining for alpha-dystroglycan. Genetic analysis, performed in spite of normal alpha-dystroglycan muscle analysis on Western Blot, disclosed a homozygote C826A (Leu276Ileu) point mutation in the fukutin-related protein (FKRP) gene, which is the most frequent mutation found in limb girdle muscular dystrophy (LGMD) type 2I. In contrast to FKRP-related congenital muscular dystrophies, LGMD2I patients most often show normal cognition and absence of brain MRI abnormalities (although several cases with cognitive deficit and/or MRI changes have been reported) [ 1 Quijano-Roy S. Martí-Carrera I. Makri S. et al. Brain MRI abnormalities in muscular dystrophy due to FKRP mutations. Brain Dev. 2006; 28: 232-242 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar , 2 Palmieri A. Manara R. Bello L. et al. Cognitive profile and MRI findings in limb-girdle muscular dystrophy 2I. J Neurol. 2011; 258: 1312-1320 Crossref PubMed Scopus (21) Google Scholar , 3 Bourteel H. Vermersch P. Cuisset J.M. et al. Clinical and mutational spectrum of limb-girdle muscular dystrophy type 2I in 11 French patients. J Neurol Neurosurg Psychiatry. 2009; 80: 1405-1408 Crossref PubMed Scopus (26) Google Scholar ]. Because of the history of seizure, a 3T brain MRI was performed, showing frontal subependymal lesions isointense to normal gray matter on all sequences consistent with cortical heterotopia, two frontal subcortical lesions isointense to normal gray matter on T1- and T2-weighted imaging and hyperintense on FLAIR sequences consistent with (sub)cortical dysplasia, and slight ventriculomegaly of the left lateral ventricle (Fig. 1).