title: Importance and challenge of making an early diagnosis in LMNA-related muscular dystrophy.
abstract: OBJECTIVE
  To identify the most useful clinical and histologic markers that facilitate early diagnosis in LMNA-related muscular dystrophy and to assess the usefulness of Western blotting (WB) for lamin A/C.
  
  
  METHODS
  We analyzed the clinical and histologic features and WB results of all patients with laminopathies diagnosed in a research-based diagnostic service over 8 years.
  
  
  RESULTS
  Although patients with congenital muscular dystrophy (MDCL) (n = 5) and Emery-Dreifuss muscular dystrophy (EDMD) (n = 5) had distinctive early clinical features, the lack of a suggestive clinical phenotype significantly delayed diagnosis in 2 of 3 patients with limb-girdle muscular dystrophy (LGMD) (n = 3). In addition, 6 of 20 muscle biopsy samples were considered nondystrophic, which contributed to delays in diagnosis in some patients. Neck extensor involvement (weakness or contractures) was the most consistent clinical sign, present in all patients. Reduced lamin A/C levels on WB were seen in 5 of 9 patients with laminopathies.
  
  
  CONCLUSIONS
  Clinical features provide the best clues for diagnosing MDCL and EDMD early in the disease, and we urge clinicians to become familiar with those phenotypes. WB for lamin A/C may contribute to diagnosis but requires technical expertise, and results are normal in many individuals with LMNA mutations. Because of the survival benefit of early diagnosis and treatment, we recommend that LMNA gene sequencing be performed in all patients with undiagnosed congenital muscular dystrophy and neck extensor weakness, all patients with genetically undiagnosed LGMD, and those with suggestive clinical signs and nonspecific histologic abnormalities.
authors.affiliation: Institute for Neuroscience and Muscle Research, Children’s Hospital at Westmead, Sydney, Australia.
authors.forename: M P
authors.initials: MP
authors.lastname: Menezes
authors.forename: L B
authors.initials: LB
authors.lastname: Waddell
authors.forename: F J
authors.initials: FJ
authors.lastname: Evesson
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.forename: R
authors.initials: R
authors.lastname: Webster
authors.forename: K
authors.initials: K
authors.lastname: Jones
authors.forename: D
authors.initials: D
authors.lastname: Mowat
authors.forename: M C
authors.initials: MC
authors.lastname: Kiernan
authors.forename: H M
authors.initials: HM
authors.lastname: Johnston
authors.forename: A
authors.initials: A
authors.lastname: Corbett
authors.forename: M
authors.initials: M
authors.lastname: Harbord
authors.forename: K N
authors.initials: KN
authors.lastname: North
authors.forename: N F
authors.initials: NF
authors.lastname: Clarke
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003286:Contracture / Q000235:genetics* / Q000473:pathology; D042241:Early Diagnosis; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D034904:Lamin Type A / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010641:Phenotype
chemical_list: D015415:Biomarkers; C494847:LMNA protein, human; D034904:Lamin Type A; C440308:lamin C