When myopathy breaks the rules: a late-onset distal presentation.
Myopathies typically present with proximal or generalised muscle weakness, but it is important for clinicians to recognise they may also have other distributions. This paper describes a case of distal myopathy that was confirmed genetically as ZASP (Z-band alternatively spliced PDZ motif-containing protein) myofibrillar myopathy (MFM). MFMs are particularly topical because the genetic basis of several have recently been established, enabling diagnosis of conditions previously labelled 'idiopathic myopathy', and shedding new light on their pathophysiology. This paper describes a purely distal lower limb phenotype of ZASP MFM, the pathophysiology of ZASP and other MFMs, and the differential diagnosis of late-onset distal symmetrical weakness. The case includes several learning points: ZASP MFM is a new diagnosis; it should be included in differential diagnoses for late-onset myopathy, especially if there is a distal pattern or autosomal dominant inheritance; testing for cardiomyopathy is recommended, and a genetic test is now available.
Department of Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Rachel
R
Newby
Department of Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Stuart
S
Jamieson
Neuromuscular Research Center, Tampere, Finland Folkhalsan Institute of Genetics, Helsinki, Finland.
Bjarne
B
Udd
Department of Neurosciences, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Jane
J
Alty
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D049310:Distal Myopathies / Q000235:genetics / Q000503:physiopathology*; D061826:Foot Orthoses; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins / Q000235:genetics; D008297:Male; D018908:Muscle Weakness / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000473:pathology*; D020125:Mutation, Missense; D010641:Phenotype; D026741:Physical Therapy Modalities
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C120696:LDB3 protein, human; D060588:LIM Domain Proteins