Occipital cortex dysgenesis with white matter changes due to mutations in Laminin a2

Abstract

Laminin α2 related congenital muscular dystrophy is one of the most common congenital muscular dystrophies of childhood with or without clinical evidence of central nervous system involvement. It may be associated with significant white matter abnormalities resembling leukodystrophies. In this study, we elaborated on two cases with laminin α2 related congenital muscular dystrophy who had occipital cortex dysgenesis in addition to characteristic white matter abnormalities. Although laminin α2 related congenital muscular dystrophy with white matter abnormalities is known, the association with occipital cortex dysplasia has been not well recognized by clinical colleagues.Key words: laminin α2, congenital muscular dystrophy, occipital cortex, dysgenesis.The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) -referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) to mild, later childhood-onset limb-girdle type muscular dystrophy as late-onset LAMA2-related muscular dystrophy (LAMA2 MD) 1 . LAMA2 Laminin α2 related CMD is caused by the mutations in the LAMA2 gene (OMIM 607855) located on chromosome 6q22-23 coding the α2 chain of laminin-211, also known as merosin, a heterotrimeric extracellular matrix protein 2 . It is one of the most common forms of CMD. Patients present with hypotonia, weakness of the extremities and contractures in the distal extremities. Patients with complete deficiency do not achieve independent ambulation but patients with a partial deficiency present with milder phenotypes 1,2 . Most of the patients have abnormal brain magnetic resonance imaging (MRI), which consists of high signal on T2 weighted and FLAIR images 1,2 . Malformations of cortical development mainly involving the occipital cortex have been not well appreciated in clinical practice to be associated with laminin α2 related congenital muscular dystrophy 3-9 . Case Reports Case 1A four-month-old boy was admitted for the investigation of delayed motor milestones. Birth history was unremarkable. Parents were second-degree consanguineous and he had a healthy four-year-old sister. He was not able to hold his head. He was hypotonic and deep tendon reflexes could not be obtained. Serum creatinine kinase was elevated with 4267 IU/L. Congenital muscular dystrophy was suggested and the patient was referred for ophthalmologic examination and brain magnetic resonance imaging (MRI) scans. Ophthalmologic examination was normal but brain MRI revealed occipital cortical dysgenesis with a subcortical band heterotopia (Fig. 1a).