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Infantile myofibromatosis (IM) is a rare disorder characterized by the development of benign tumors in the skin, muscle, bone, and viscera. The incidence is 1/150,000 live births and the disease is the most common cause of fibrous tumors in infancy. Cases which lack visceral involvement generally have a more benign course, usually with spontaneous regression of the tumors. On the other hand, the prognosis tends to be unfavorable when there is involvement of vital organs, which can lead to significant mortality. The identification of rare variants in genes that may cause IM is the first step towards the possibility of targeted treatments; however, the molecular pathogenesis of IM is poorly understood. In the present study, we report the results of exome sequence analysis of two brothers diagnosed with visceral multicentric infantile myofibromatosis, and their healthy consanguineous parents. In the two brothers we identified novel homozygous variants in NDRG4 gene (N-myc downregulated gene family member 4) and in RLTPR gene (RGD motif, leucine rich repeats, tropomodulin domain and proline-rich containing). The healthy parents were heterozygous for both variants. Consistent with the phenotype of IM, NDRG4 is a tumor-related gene; its expression has been shown to be decreased in numerous tumor types, suggesting that it might be a tumor suppressor gene. Additionally, studies have demonstrated that NDRG4 may have a role in cell survival and tumor invasion. We thus propose that this homozygous variant in NDRG4 may be the causative variant of the autosomal recessive form of IM in the studied family and that it should be investigated in other cases of autosomal recessive infantile myofibromatosis. [ABSTRACT FROM AUTHOR]

Infantile myofibromatosis, the most common fibrous tumor of infancy, occurs in solitary, multiple, and generalized forms, with similar histology but different clinicopathologic and prognostic implications. This entity is a mesenchymal disorder characterized by the proliferation of fibrous tumors in the skin, muscles, viscera, bones, and subcutaneous tissues. Visceral lesions are associated with significant morbidity and mortality, generally within the first few months of life. They lead to failure to thrive, to infection, hemorrhage, or to the obstruction of vital organs. We describe two cases of multicentric myofibromatosis with significant in utero lesional growth, resulting in one fetal demise and one post-natal demise. To the best of our knowledge, this is the first report of a fetal death secondary to infantile myofibromatosis. [ABSTRACT FROM AUTHOR]

A typical case of congenital generalized fibromatosis (CGF) is presented and the literature on this entity is reviewed. CGF is a rare condition which is probably heritable. It is manifested in infancy. Because of the unusual biological behavior of the fibromata, two clinical courses occur-death, if vital viscera are involved, or regression of the lesions and survival without significant disability. Including the present example, 63 cases have been reported. [ABSTRACT FROM AUTHOR]