title: Ullrich congenital muscular dystrophy: connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes.
abstract: Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in the three genes coding for the alpha chains of collagen VI and characterized by generalized muscle weakness, striking hypermobility of distal joints in conjunction with variable contractures of more proximal joints, and normal intellectual development. The diagnosis is supported by abnormal immunoreactivity for collagen VI on muscle biopsies. As patients with UCMD show clinical characteristics typical of classical disorders of connective tissue such as Ehlers-Danlos syndromes (EDS), we investigated the ultrastructure of skin biopsy samples from patients with UCMD (n=5). Electron microscopy of skin biopsies revealed ultrastructural abnormalities in all cases, including alterations of collagen fibril morphology (variation in size and composite fibers) and increase in ground substance, which resemble those seen in patients with EDS. Our findings suggest that there is a true connective tissue component as part of the phenotypic spectrum of UCMD and that there is considerable clinical as well as morphological overlap between UCMD and classic connective tissue disorders.
authors.affiliation: Division of Neurology, The Children's Hospital of Philadelphia, and University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Janbernd
authors.initials: J
authors.lastname: Kirschner
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hausser
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zou
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schreiber
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Christen
authors.forename: Susan C
authors.initials: SC
authors.lastname: Brown
authors.forename: Ingrun
authors.initials: I
authors.lastname: Anton-Lamprecht
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Folker
authors.initials: F
authors.lastname: Hanefeld
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
mesh_terms: D000293:Adolescent; D002648:Child; D003238:Connective Tissue / Q000002:abnormalities*; D003937:Diagnosis, Differential; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis*; D006801:Humans; D008854:Microscopy, Electron; D009136:Muscular Dystrophies / Q000151:congenital / Q000175:diagnosis*; D012867:Skin / Q000473:pathology* / Q000648:ultrastructure