Capillary morphogenesis gene-2 mutation in infantile systemic hyalinosis: ultrastructural study and mutation analysis in a Taiwanese infant

Infantile systemic hyalinosis (ISH) is a very rare infantile stiff-skin syndrome characterized by extensive deposits of hyaline material in various organs, especially the skin and gingiva. Recent studies identified pathogenic mutations in the capillary morphogenesis gene 2 (CMG2) in both ISH and juvenile hyaline fibromatosis (JHF). Capillary morphogenesis protein-2 is an integrin-like cell surface receptor for laminins and type IV collagen, and may play a key role in cell-matrix or cell-cell interactions. We report a case of ISH in a 13-month-old Taiwanese girl who manifested progressive joint contractures, recurrent chest infections, chronic diarrhoea with severe hypoalbuminemia and ascites, gum hypertrophy, and violaceous papules and nodules over the occipital area, neck, lumbosacral and anogenital areas since birth. Skin biopsy revealed a thickened and hyalinized papillary dermis. Electron microscopy showed abundant extracellular fibrillogranular material and active fibroblasts with conspicuous Golgi complex filled with fibrillar material. Mutation analysis identified a homozygous 1073-1074insC mutation of CMG2 which had been reported in four other families and may represent a mutation hot spot.