Table 1.
Summary of the clinical and radiologic features observed in MDA5 mutation-positive patients from families 1938 and 1972*
| Family 1938 patient 1 | Family 1938 patient 2 | Family 1938 patient 3 | Family 1972 patient 1 | Family 1972 patient 2 | |
|---|---|---|---|---|---|
| Mutation | c.992C>T/p.Thr331Ile | c.992C>T/p.Thr331Ile | c.992C>T/p.Thr331Ile | c.992C>G/p.Thr331Arg | c.992C>G/p.Thr331Arg |
| Sex | Female | Female | Female | Female | Male |
| Age at onset, years | Early infancy | 6 | 3 | 8 | 11 |
| Current age, years | 18 | 45 | 27 | 9 | 47 |
| Height at last contact, cm/age, years/SD of mean height | 146/18/—2 | 145/45/−3 | 144/27/−3 | 125/9/0 | NR |
| Features at presentation | Gluteal fistula, muscle weakness, joint pain | Joint pain | Joint pain | Muscle weakness and leg pain | Glaucoma |
| Aero-osteolysis | Yes | Yes | Yes | Yes | Yes |
| Joint subluxation | Yes | Yes | Yes | No | Yes |
| Tendon rupture | No | No | No | No | Yes (quadriceps, bilateral, at ages 34 and 35 years) |
| Periarticular calcifications | Yes | Yes | Yes | No | No |
| Abnormal dentition | Yes (delayed eruption of primary and secondary dentition) | Yes (loss of teeth in adolescence leading to use of prosthesis) | Yes (loss of teeth in adolescence leading to use of prosthesis) | Delayed eruption of secondary dentition | Yes (delayed tooth eruption and early loss of secondary dentition with resorption of dental roots) |
| Glaucoma (age at diagnosis, years) | No | No | No | No | Yes (11) |
| Aortic/cardiac valve calcification | No | Yes | Yes | No | NA |
| Cardiac status | Hypertension, concentric LVH, mild left atrial and aortic root dilation with aortic valve insufficiency | Hypertension, LVH, aortic valve stenosis | Aortic valve calcification | No abnormalities | NA |
| Psoriasiform rash (age at onset, years) | Yes (13) | No | Yes (21) | No | Yes (early adulthood) |
| Multiple lentigines | Yes | Yes | No | No | Yes |
| Basal ganglia calcification | Yes | Yes | Yes | No cerebral imaging | No cerebral imaging |
| High hairline/broad forehead | Yes | Yes | Yes | Yes | Yes |
| Prominent muscle weakness | Yes, as infant with myopathic changes on muscle biopsy | No | No | Yes, as infant | No |
| IFN score (age, years)† | 29.7 (18) | 15.1 (45) | 16.9 (27) | 14.0 (9) | 18.8 (47) |
| Markers of inflammation/ autoantibodies | ESR and CRP normal; autoantibody (ANA and anti-dsDNA) and RF negative; HLA-B27 positivity; C3 and C4 normal | ESR and CRP normal; autoantibody (ANA, anti-dsDNA, Sm/ RNP, and Scl-70) and RF negative; C3 and C4 normal | NR | ESR and CRP normal; mildly elevated anti-dsDNA antibodies on 1 occasion; ANA, anti-MDA5 and anti-CCP antibodies negative; RF negative; monocyte CD169/Siglec-1 expression increased; C3 slightly reduced, C4 normal | ESR and CRP normal; RF increased; elevated ANA, anti-CCP, anti-SSA/Ro, and anti-angiotensin II type 1 antibodies; anti-dsDNA antibodies normal; monocyte CD169/ Siglec-1 expression increased; C3 and C4 normal |
*
NR = not recorded; NA = not assessed; LVH = left ventricular hypertrophy; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; ANA = antinuclear antibody; anti-dsDNA = anti-double-stranded DNA; RF = rheumatoid factor; anti-CCP = anti-cyclic citrullinated peptide; Siglec-1 = sialic acid-binding Ig-like lectin 1.
†
Interferon (IFN) scores of >2.466 are considered abnormal.