ORPHA: 2591; DO: 0080109;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.12 | ?Myofibromatosis, infantile 2 | 615293 | Autosomal dominant | 3 | NOTCH3 | 600276 |
A number sign (#) is used with this entry because of evidence that infantile myofibromatosis-2 (IMF2) is caused by heterozygous mutation in the NOTCH3 gene (600276) on chromosome 19p13. One such family has been reported.
Infantile myofibromatosis is a disorder of mesenchymal proliferation characterized by the development of benign tumors in the skin, muscle, bone, and viscera. Soft tissue lesions may regress spontaneously. Visceral lesions are associated with high morbidity and mortality (summary by Martignetti et al., 2013).
For a discussion of genetic heterogeneity of infantile myofibromatosis, see IMF1 (228550).
Martignetti et al. (2013) reported a 2-generation family (IM-9) in which 9 individuals had infantile myofibromatosis. Histopathologic examination of a soft tissue tumor isolated from this family was consistent with the diagnosis. No additional clinical information was provided, except that the family had multiple, recurrent, soft tissue lesions and no evidence of CADASIL (125310).
The transmission pattern of IMF2 in the family reported by Martignetti et al. (2013) was consistent with autosomal dominant inheritance.
In affected members of a family with IMF2, Martignetti et al. (2013) identified a heterozygous mutation in the NOTCH3 gene (L1519P; 600276.0012). The mutation, which was identified by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder and was not found in several large control databases. No functional studies were performed, but the authors predicted that the mutation would result in hyperactivation of NOTCH3.
Martignetti, J. A., Tian, L., Li, D., Ramirez, M. C. M., Camacho-Vanegas, O., Camacho, S. C., Guo, Y., Zand, D. J., Bernstein, A. M., Masur, S. K., Kim, C. E., Otieno, F. G., and 16 others. Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am. J. Hum. Genet. 92: 1001-1007, 2013. [PubMed: 23731542] [Full Text: https://doi.org/10.1016/j.ajhg.2013.04.024]