Pediatric-onset inflammatory
myositis (IM) and
systemic lupus erythematosus (SLE) are rare inflammatory diseases. Both result from the complex interaction of genetic and environmental factors. An increasing number of Mendelian conditions predisposing to the development of SLE have been recently identified. These include monogenic conditions, referred to as the type I interferonopathies, associated with a primary upregulation of
type I interferon (IFN), a key
cytokine in the pathogenesis of SLE and some cases of IM. Here, we report on a pediatric-onset inflammatory overlap phenotype in a 6-year-old girl who was shown to carry
mosaic tetrasomy 9p. The patient presented with
myositis overlapping with lupuslike features.
Myositis was characterized by a proximal
muscular weakness and HLA
class I antigen myofiber overexpression on muscle biopsy. Lupus-like manifestations consisted of
pericarditis,
pleuritis, and positive antinuclear and anti-SSA (Sjögren-syndrome A)
antibodies. Complete remission was achieved with
corticosteroids and mycophenolate mofetyl. Analysis of
tetrasomy 9p showed mosaic
tetrasomy in the 9p24.3q12 region, including the type I IFN cluster, and increased expression of IFN-stimulated genes. These data suggest that
mosaic tetrasomy 9p can be associated with an upregulation of type I IFN signaling, predisposing to inflammatory
myositis and lupus-like features. Thus, unexplained muscle or other organ involvement in patients carrying mosaic
tetrasomy of the type IFN cluster of chromosome 9p should lead to the search for IM and/or lupuslike disease, and karyotype should be performed in patients with SLE or IM with
mental retardation.