Exuberant Juvenile Hyaline Fibromatosis in Two Patients Mariela Lea˜ o Muniz, M.D.,* Alice Zoghbi Coelho Lobo, M.D.,* Maria Cecı´lia da Matta Rivitti Machado, M.D.,* Neusa Yuriko Sakai Valente, M.D.,* Chong Ae Kim, M.D., Sı´lvia Vanessa Lourenc¸o, D.D.S., Ph.D.,* and Marcello Menta Simonsen Nico, M.D.* *Department of Dermatology, Hospital das Clı´nicas, University of Sa ˜o Paulo School of Medicine, Sa ˜o Paulo,  Clinical Genetics, Department of Pediatrics, Instituto da Crianc ¸ a, University of Sa ˜o Paulo, Sa ˜o Paulo, Brazil Abstract: Juvenile hyaline fibromatosis and infantile systemic hyalinosis are rare autosomal recessive disorders of infancy and early childhood that are histologically characterized by deposition of hyaline material. The main clinical features are papulo-nodular skin lesions, gingival hypertrophy, joint contractures, and bone abnormalities. However, infantile systemic hyalino- sis has a more severe clinical presentation, including visceral involvement and premature death. Very recently, genetic studies identified mutations in the same gene in patients with both conditions, strongly suggesting that they belong to the same disease spectrum. We report two new nonrelated patients who met the criteria for the diagnosis of juvenile hyaline fibroma- tosis/infantile systemic hyalinosis. Clinical, histopathologic, immunohisto- chemical, and ultrastructural findings are presented, as well as an extensive review of the literature. Recent information regarding pathogenesis and treatment is discussed. Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) represent the rare multifocal childhood fibromatoses that are characterized by the production and deposition of an unidentified hyaline material in the skin and other organs. Both syndromes are considered autosomal recessive conditions and are characterized by multiple skin lesions, gingival hypertrophy, joint contractures, osteolysis, and osteoporosis (1). Onset of JHF occurs within the first few years of life, and most patients described have survived into adulthood (2), with the oldest reported survivor being 51 years old (3). ISH is distinguished from JHF by a clinically more severe presentation that includes hyperpigmented plaques over the joints, visceral involvement, diarrhea, recurrent infections, and death within the first 2 years of life. Originally described as two distinct entities, JHF and ISH are now considered part of the same disease spec- trum, as recent genetic studies have demonstrated mutations in the same gene in patients with both condi- tions. CASE REPORTS Patient 1 A Brazilian boy was born to a healthy consanguineous couple after an unremarkable pregnancy and delivery. He was normal at birth, but at 2 months of age his mother noticed that he could not extend his legs com- pletely and that his joints seemed thickened. A few months later, the first skin lesions were seen. Address correspondence to Alice Zoghbi Coelho Lobo, Av. Dracena, 21 Residencial Tambore´ 1, 06458-140 Barueri, Sa˜o Paulo, Brazil, or e-mail: loboalice@hotmail.com. 458 2006 The Authors. Journal compilation Ó 2006 Blackwell Publishing, Inc. Pediatric Dermatology Vol. 23 No. 5 458–464, 2006