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Infantile systemic hyalinosis

Synonym(s) -
Prevalence <1 / 1 000 000
Inheritance Autosomal recessive
Age of onset Antenatal
  • E78.8
MeSH -
MedDRA -


Disease definition

Infantile systemic hyalinosis (ISH) is a very rare disorder belonging to the heterogeneous group of genetic fibromatoses and is characterized by progressive joint contractures, skin abnormalities, severe chronic pain and widespread deposition of hyaline material in many tissues such as the skin, skeletal muscle, cardiac muscle, gastrointestinal tract, lymph nodes, spleen, thyroid, and adrenal glands.


Less than 20 cases have been described in the literature so far.

Clinical description

The clinical features are evident either at birth or within the first six months of life. Intrauterine growth retardation and reduced fetal movements have been described in some ISH patients. The main clinical features are painful swollen joint contractures, significant discomfort on handling and reduction of spontaneous movement. Dermal abnormalities include diminished skin elasticity, generalized skin thickening with hyperpigmentation over prominences, small pearly papules (predominantly on the face, scalp, and neck), massive gingival hypertrophy, and fleshy nodules in the perianal region. Susceptibility to infections and intractable diarrhea are common findings. Failure to thrive is characteristic. Osteopenia is often present and results in increased susceptibility to bone fractures. Children with ISH are intellectually normal.


ISH is caused by mutations in anthrax toxin receptor 2 gene (ANTRX2) on chromosome 4q21. Mutations in the same gene cause juvenile hyaline fibromatosis, a similar but milder disease (see this term).

Diagnostic methods

Diagnosis is clinical and can be further supported by histological evidence of deposition of amorphous hyaline material in the skin or mucosae.

Differential diagnosis

Juvenile hyaline fibromatosis, Winchester syndrome, lipoid proteinosis (Urbach-Wiethe disease) and mucopolysaccharidosis type II (Hunter's syndrome) should be considered in the differential diagnosis (see these terms).

Genetic counseling

ISH is transmitted as an autosomal recessive trait.

Management and treatment

There is no specific treatment for ISH. Physical therapy and nutritional support improve the quality of life of the patients.


ISH has a progressive course that may lead to death within the first two years of life, mostly due to recurrent respiratory infections and severe diarrhea. In patients that live until adulthood, mobility remains severely restricted by joint contractures.

Expert reviewer(s)

  • Dr Luciano MERLINI

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Detailed information

Clinical genetics review
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