Congenital muscular dystrophy with laminin alpha 2 chain deficiency: identification of a new intermediate phenotype and correlation of clinical findings to muscle immunohistochemistry.
The laminins comprise of a family of heterotrimeric proteins of the extracellular matrix. The crossshaped proteins consist of a heavy alpha-chain and two light chains, called beta and gamma. Each group of chains, classified on their sequence identity and domain organization, include different isoforms. A deficiency of the alpha 2 chain of laminin-2, previously termed merosin or M component, was shown to be responsible for one form of congenital muscular dystrophy (CMD). We investigated muscle biopsies of 20 patients with the clinical diagnosis of CMD and histological evidence of muscular dystrophy for the expression of different laminin chains. Patients with evidence of pachygyria/lissencephaly of the CNS were excluded from this series. The immunohistochemical analysis was correlated to clinical findings and MRI data of the brain. Of 20 patients, 11 (55%) revealed complete or near-complete deficiency of the alpha 2 chain in their skeletal muscle specimens. So far none of these patients became ambulant. Of 20 patients 2 showed partial but clear-cut alpha 2 chain-deficiency. These two patients became ambulant at 18 months and 3 years. All 13 patients with complete or partial alpha 2 chain-deficiency demonstrated cerebral white matter changes on MRI. In contrast, 6/7 CMD patients with normal alpha 2 chain expression became ambulant and none of the 6/7 tested showed evidence of cerebral abnormal T2 sequence signal of the myelin on MRI.


CONCLUSIONS
Our findings emphasize the use of immunohistochemistry for laminin alpha 2 as a diagnostic tool in defining CMD and characterize a milder phenotype with partial alpha 2 chain-deficiency.
Department of Paediatrics, University of Essen, Germany.
R
R
Herrmann
V
V
Straub
K
K
Meyer
T
T
Kahn
M
M
Wagner
T
T
Voit
D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000172:deficiency / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype
D007797:Laminin