Caffey Disease

Posted September 23, 2022 by Anusha ‐ 3 min read

Caffey disease, also called infantile cortical hyperostosis, is a bone disorder that most often occurs in babies. Excessive new bone formation (hyperostosis) is characteristic of Caffey disease. Caffey disease is characterized by massive subperiosteal new bone formation (usually involving the diaphyses of the long bones as well as the ribs, mandible, scapulae, and clavicles) typically associated with fever, joint swelling, and pain in children, with onset between birth and five months and spontaneous resolution by age two years.

Other names of Caffey Disease

  • Caffey-Silverman syndrome

  • De Toni-Caffey disease

  • Infantile cortical hyperostosis

Causes of Caffey Disease

  • A mutation in the COL1A1 gene causes Caffey disease.

  • The COL1A1 gene provides instructions for making part of a large molecule called type I collagen.

  • Collagens are a family of proteins that strengthen and support many tissues in the body, including cartilage, bone, tendon, and skin. In these tissues, type I collagen is found in the spaces around cells.

  • The collagen molecules are cross-linked in long, thin, fibrils that are very strong and flexible.

  • Type I collagen is the most abundant form of collagen in the human body.

  • The COL1A1 gene mutation that causes Caffey disease replaces the protein building block (amino acid) arginine with the amino acid cysteine at protein position 836 (written as Arg836Cys or R836C).

  • This mutation results in the production of type I collagen fibrils that are variable in size and shape, but it is unknown how these changes lead to the signs and symptoms of Caffey disease.

Symptoms of Caffey Disease

  • Clinical findings of irritability, fever, and/or pallor accompanied by soft-tissue swelling and pain adjacent to involved bones

  • Radiologic findings of subperiosteal cortical hyperostosis of the diaphyses of the long bones (with sparing of the epiphyses), as well as the ribs, scapulae, clavicles, and mandible

  • Findings typically appearing between birth and age five months and resolving spontaneously by age two years, although recurrence in adolescence is possible

Diagnosis of Caffey Disease

  • Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype.

  • Single-gene testing - Sequence analysis of COL1A1 detects small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected.

  • In rare cases, skeletal abnormalities can be detected by ultrasound imaging during the last few weeks of development before birth.

  • Ultrasound can identify soft tissue edema and early periosteal new bone formation.

  • High-frequency transducers should be used.

  • MRI can show periostitis and soft tissue edema.

  • It should be stressed that MRI usually does not offer much added-value in advancing the diagnosis 5 unless infection or neoplasia are high on the differential list; indeed, at times, MRI appearance may confound the radiologist.

  • Hence, radiography should be the primary modality of investigation and follow-up.

  • Nuclear imaging during the active phase of the disease, there is markedly increased radiotracer uptake in the involved bones, both on bone and gallium (Ga-67) scans.

  • The bearded infant appearance refers to intense radiotracer uptake in the mandible.

Treatment of Caffey Disease

  • No specific treatment exists for infantile cortical hyperostosis (Caffey disease).

  • The disease is self-limited and usually resolves without sequelae.

  • Some periods of exacerbation and remission may occur during the course of this condition

  • Symptomatic treatment consists of NSAIDs, e.g. indomethacin.

diseases disorders caffey-disease

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