Ullrich congenital muscular dystrophy and Bethlem myopathy: clinical and genetic heterogeneity

Abstract

Ullrich congenital muscular dystrophy (UCMD), due to mutations in the collagen VI genes, is an autosomal recessive form of CMD, commonly associated with distal joints hyperlaxity and severe course. A mild or moderate involvement can be occasionally observed.

Objective: To evaluate the clinical picture of CMD patients with Ullrich phenotype who presented decreased or absent collagen VI immunoreactivity on muscular biopsy.

Results: Among 60 patients with CMD, two had no expression of collagen V and their clinical involvement was essentially different: the first (3 years of follow-up) has mild motor difficulty; the second (8 years of follow-up) never acquired walking and depends on ventilatory support. A molecular study, performed by Pan et al. at the Thomas Jefferson University, demonstrated in the first a known mutation of Bethlem myopathy in COL6A1 and in the second the first dominantly acting mutation in UCMD and the first in COL6A1, previously associated only to Bethlem myopathy, with benign course and dominant inheritance.

Conclusion: Bethlem myopathy should be considered in the differential diagnosis of UCMD, even in patients without fingers contractures; overlap between Ullrich and Bethlem phenotypes can be supposed.