''Classic'' congenital muscular dystrophy is a heterogeneous group of
disorders, characterized by early-onset muscle weakness and hypotonia,
absence of overt cerebral or ocular symptoms, and muscle pathology co
nsistent with a dystrophic process. A subset of patients with congenit
al muscular dystrophy have recently been found to be deficient in the
extra-cellular matrix protein merosin. Consequently, we reviewed the c
linical, pathologic, and immunohistochemical features of 12 patients (
six males and six females) with classic congenital muscular dystrophy
who have been seen at the Children's Hospital, Boston, over the past 1
5 years. There was marked clinical heterogeneity within this patient p
opulation, with age of independent ambulation ranging from 13 months t
o 6 years. Immunocytochemical analysis using; antibodies to merosin, d
ystrophin, 43-kDa dystroglycan, adhalin, and laminin was normal in 11
of 12 patients. One patient had markedly abnormal staining for merosin
; the majority of fibers were negative, although occasional fibers dem
onstrated patchy staining. Immunoblot analysis in this patient demonst
rated markedly reduced levels of merosin (< 10% compared to controls a
nd other patients), of apparently normal size. Clinically this patient
could be differentiated from the others by a marked elevation of seru
m creatine kinase (> 1000 U/L) and the presence of early white-matter
changes on magnetic resonance imaging. The results of this study suppo
rt the observation that abnormalities of merosin are present in a subg
roup of patients with classic congenital muscular dystrophy. Although
marked elevation of serum creatine kinase and white-matter changes on
magnetic resonance imaging may serve to distinguish these patients fro
m other patients with congenital muscular dystrophy, there remains a l
arge proportion of patients in whom the underlying pathogenesis remain
s to be elucidated.