Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy

Arthritis Rheum. 1998 Apr;41(4):710-9. doi: 10.1002/1529-0131(199804)41:4<710::AID-ART19>3.0.CO;2-K.


Objective: To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM.

Methods: Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familial IIM were compared with those in 181 patients with sporadic IIM. The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 2 families with inclusion body myositis.

Results: The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies was lower in familial than in sporadic IIM. DRB1*0301 was a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM). Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002).

Conclusion: These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Alleles
  • Autoantibodies / blood
  • Child
  • Dermatomyositis / blood
  • Dermatomyositis / genetics
  • Dermatomyositis / immunology
  • Family Health
  • Female
  • HLA Antigens / blood
  • HLA-DQ Antigens / blood
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DR Antigens / blood
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Immunoglobulin Allotypes / blood
  • Immunoglobulin Allotypes / genetics
  • Immunoglobulin Gm Allotypes / blood
  • Immunoglobulin Gm Allotypes / genetics
  • Male
  • Middle Aged
  • Myositis / blood
  • Myositis / genetics*
  • Myositis / immunology*
  • Myositis, Inclusion Body / blood
  • Myositis, Inclusion Body / genetics
  • Myositis, Inclusion Body / immunology
  • Pedigree
  • Phenotype
  • Reference Values


  • Autoantibodies
  • HLA Antigens
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*03:01 antigen
  • Immunoglobulin Allotypes
  • Immunoglobulin Gm Allotypes