title: Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures.
abstract: Limb girdle muscular dystrophy 2A is a common variant secondary to mutations in the calpain 3 gene. A proportion of patients has early and severe contractures, which can cause diagnostic difficulties with other conditions. We report clinical and muscle magnetic resonance imaging findings in seven limb girdle muscular dystrophy 2A patients (four sporadic and three familial) who had prominent and early contractures. All patients showed a striking involvement of the posterior thigh muscles. The involvement of the other thigh muscles was variable and was related to clinical severity. Young patients with minimal functional motor impairment showed a predominant involvement of the adductors and semimembranosus muscles while patients with restricted ambulation had a more diffuse involvement of the posterolateral muscles of the thigh and of the vastus intermedius with relative sparing of the vastus lateralis, sartorius and gracilis. At calf level all patients showed involvement of the soleus muscle and of the medial head of the gastrocnemius with relative sparing of the lateral head. MRI findings were correlated to those found in two patients with the phenotype of limb girdle muscular dystrophy 2A without early contractures and the pattern observed was quite similar. However, the pattern observed in limb girdle muscular dystrophy 2A is different from that reported in other muscle diseases such as Emery-Dreifuss muscular dystrophy and Bethlem myopathy which have a significant clinical overlap with limb girdle muscular dystrophy 2A once early contractures are present. Our results suggest that muscle MRI may help in recognising patients with limb girdle muscular dystrophy 2A even when the clinical presentation overlaps with other conditions, and may therefore, be used as an additional investigation to target the appropriate biochemical and genetic tests.
authors.affiliation: Department of Paediatrics and Neonatal Medicine, Dubowitz Neuromuscular Centre, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. e.mercuri@imperial.ac.uk
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.forename: Daniel
authors.initials: D
authors.lastname: Birchall
authors.forename: Marika
authors.initials: M
authors.lastname: Pane
authors.forename: Maria
authors.initials: M
authors.lastname: Kinali
authors.forename: Joanna
authors.initials: J
authors.lastname: Allsop
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nigro
authors.forename: Amets
authors.initials: A
authors.lastname: Sáenz
authors.forename: Annachiara
authors.initials: A
authors.lastname: Nascimbeni
authors.forename: Luigi
authors.initials: L
authors.lastname: Fulizio
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002154:Calpain / Q000172:deficiency* / Q000235:genetics; D003286:Contracture / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency* / Q000235:genetics; D007866:Leg / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype
chemical_list: D007527:Isoenzymes; D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain