Infantile systemic hyalinosis

Infantile systemic hyalinosis (ISH), also known as hyaline fibromatosis syndrome (severe form), is an extremely rare and severe autosomal recessive disorder caused by mutations in the ANTXR2 gene (also known as CMG2), which encodes a transmembrane protein involved in extracellular matrix homeostasis. The disease is characterized by the widespread deposition of hyaline (amorphous, glassy) material in multiple tissues throughout the body. ISH represents the more severe end of the spectrum of hyaline fibromatosis syndrome, with juvenile hyaline fibromatosis being the milder form. Clinical features typically manifest in the first few months of life and include painful joint contractures, diffuse skin thickening and hyperpigmentation, gingival hypertrophy, subcutaneous nodules or papules (particularly perianal), and failure to thrive. Affected infants often experience severe protein-losing enteropathy leading to chronic diarrhea, recurrent infections, and progressive wasting. Bone involvement includes osteopenia and osteolytic lesions. The skin lesions are often pearly papules distributed over the face, scalp, ears, and perianal region. Visceral organs may also be affected by hyaline deposits. The prognosis for infantile systemic hyalinosis is generally poor, with most affected children dying within the first two years of life due to recurrent infections, sepsis, or severe malnutrition related to protein-losing enteropathy. There is currently no curative treatment available. Management is supportive and symptomatic, focusing on pain control, nutritional support, physical therapy to manage joint contractures, and surgical excision of nodules when they cause functional impairment. Genetic counseling is recommended for affected families.

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