The clinical features of merosin-positive congenital muscular dystrophy (CMD) and merosin-deficient CMD are well known, with those of merosin-deficient CMD being more severe. Whether the severity of histopathological findings correlates with these clinical features remains unanswered. In this study, the clinical and histopathological findings of 39 merosin-deficient and 37 merosin-positive CMD patients were compared. Merosin-deficient CMD patients were found to be younger, with earlier onset of symptoms, age of diagnosis, and a more severe clinical state (reflecting maximum motor capacity and contractures). On histopathological evaluation, endomysial fibrosis, perimysial fibrosis, and histopathological state (reflecting fibrosis, adiposis, necrosis, and variation in fiber size) were more severe in merosin-deficient CMD. There was a correlation between clinical and histopathological states only in merosin-deficient CMD.
ToméFMS, EvangelistaT, LeclercA, Congenital muscular dystrophy with merosin deficiency. C R Acad Sci Paris III1994;317:351–357.
5.
Castro-GagoM, Díaz-CardamaI, MonasterioL, FusterM, Pérez-BecerraE, PeñaJ.Congenital muscular dystrophy with central nervous system involvement: an intermediate form?The Annals1985;7:5–12.
6.
DubowitzV.22nd ENMC sponsored workshop on congenital muscular dystrophy held in Baarn, The Netherlands, 14–16 May 1993 (workshop report). Neuromusc Disord1994;4:75–81.
7.
DubowitzV, FardeauM.Proceedings of the 27th ENMC sponsored workshop on congenital muscular dystrophy, 22–24 April 1994, The Netherlands (workshop report). Neuromusc Disord1995;5:253–258.
8.
DubowitzV.50th ENMC international workshop: congenital muscular dystrophy, 28 February 1997 to 2 March 1997, Naarden, The Netherlands (workshop report). Neuromusc Disord1997;7:539–547.
HillaireD, LeclercA, FauréS, Localization of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping. Hum Mol Genet1994;3:1657–1661.
11.
Helbling-LeclercA, TopalogluH, TomeFMS, Readjusting the localization of merosin (laminin α2-chain) deficient congenital muscular dystrophy locus on chromosome 6q2. C R Acad Sci Paris III1995;318:1245–1252.
12.
GuicheneyP, VignierN, Helbling-LeclercA, Genetics of laminin α2 chain (or merosin) deficient congenital muscular dystrophy: from identification of mutations to prenatal diagnosis. Neuromusc Disord1997;7:180–186.
13.
Helbling-LeclercA, ZhangX, TopalogluH, Mutations in the laminin α2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet1995; 11:216–218.
14.
NissinenM, Helbling-LeclercA, ZhangX, Substitution of a conserved cysteine-996 in a cysteine-rich motif of the laminin α2 chain in congenital muscular dystrophy with partial deficiency of the protein. Am J Hum Genet1996;58:1177–1184.
PhilpotJ, SewryC, PennockJ, DubowitzV.Clinical phenotype in congenital muscular dystrophy: correlation with expression of merosin in skeletal muscle. Neuromusc Disord1995;5:301–305.
17.
ReedUC, MarieSK, VainzofM, Congenital muscular dystrophy with cerebral white matter hypodensity Correlation of clinical features and merosin deficiency. Brain Dev1996;18:53–58.
18.
SewryCA, NaomI, D'AlessandroM, Variable clinical phenotype in merosin-deficient congenital muscular dystrophy associated with differential immunolabelling of two fragments of the laminin α2 chain. Neuromusc Disord1997;7:169–175.
19.
MoraM, MoroniI, UzielG, Mild clinical phenotype in a 12-year old boy with partial merosin deficiency and central and peripheral nervous system abnormalities. Neuromusc Disord1996;6:377–381.
20.
HerrmannR, StraubV, MeyerK, KahnT, WagnerM, VoitT.Congenital muscular dystrophy with laminin α2 chain deficiency: identification of a new intermediate phenotype and correlation of clinical findings to muscle immunohistochemistryEur J Pediatr1996;155:968–976.
21.
TanE, TopalogluH, SewryC, Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency. Neuromusc Disord1997;7:85–89.
22.
TopalogluH, KaleG, YalnizoǧluD, Analysis of “pure” congenital muscular dystrophies in thirty-eight cases. How different is the classical type 1 from the occidental type cerebromuscular dystrophy? Neuropediatrics1994;25:94–100.
23.
FardeauM, TomeFMS. Clinical and immunocytochemical evidence of heterogeneity in classical (occidental) congenital muscular dystrophy. In: FukuyamaY, OsawaM, SaitoK, eds. Congenital Muscular Dystrophies. New York: Elsevier, 1997:79–87.
24.
KobayashiO, HayashiYArahataK, OzawaE, NonakaI.Congenital muscular dystrophy: clinical and pathologic study of 50 patients with the classical (occidental) merosin-positive form. Neurology1996;46:815–818.
25.
TopalogluH, TalimB, VignierN, Merosin-deficient congenital muscular dystrophy with severe mental retardation and normal cranial MRI: a report of two siblings. Neuromusc Disord1998;8:169–174.
26.
EchenneB, RivierF, JellaliAJ, AzaisM, MornetD, PonsF.Merosin positive congenital muscular dystrophy with mental deficiency, epilepsy and MRI changes in the cerebral white matter. Neuromusc Disord1997;7:187–190.
27.
De StefanoN, DottiMT, VillanovaM, ScaranoG, FedericoA.Merosin positive congenital muscular dystrophy with severe involvement of the central nervous system. Brain Dev1996;18:323–326.
28.
AfifiA, ZellwegerH, McCormickWF, MergnerW.Congenital muscular dystrophy: light and electron microscopic observations. J Neurol Neurosurg Psychiatry1969;32:273–280.
29.
KihiraS, NonakaI.Congenital muscular dystrophy, a histochemical study with morphometric analysis on biopsied muscles. J Neurol Sci1985;70:139–149.
30.
LeytenQH, ter LaakHJ, GabreëlsFJM, RenierWO, RenkawekK, SengersRCA. Congenital muscular dystrophy, a study on the variability of morphological changes and dystrophin distribution in muscle biopsies. Acta Neuropathol1993;86:386–392.
HantaïD, Labat-RobertJ, GrimaudJA, FardeauM.Fibronectin, laminin, type I, III and IV collagens in Duchenne's muscular dystrophy, congenital muscular dystrophies and congenital myopathies: an immunocytochemical study. Connect Tissue Res1985;13:273–281.
35.
Ibraghimov-BeskrovnayaO, ErvastiJM, LeveilleCJ, SlaughterCA, SernettSW, CampbellKP. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature1992;355:696–702.
36.
ErvastiJM, CampbellKP. A role for the dystrophin–glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol1993;122:809–823.
37.
WortonR.Muscular dystrophies: diseases of the dystrophin—glycoprotein complex. Science1995;270:755–756.
38.
MendellJR, SahenkZ, PriorTW. The childhood muscular dystrophies: diseases sharing a common pathogenesis of membrane instability. J Child Neurol1995;10:150–159.
39.
MatsumuraK, CampbellKP. Dystrophin–glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophies. Muscle Nerve1994;17:2–15.
40.
ParanoE, FiumaraA, FalsaperlaR, VitaG, TrifilettiRR. Congenital muscular dystrophy: correlation of muscle biopsy and clinical features. Pediatr Neurol1994;10:233–236.
