Infantile Cortical Hyperostosis (Caffey Disease)

Updated: Sep 15, 2016
  • Author: Cara Novick, MD; Chief Editor: Harris Gellman, MD  more...
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Overview

Background

In 1945, Caffey first described infantile cortical hyperostosis (Caffey disease), a self-limited disorder that affects infants and causes bone changes, soft-tissue swelling, and irritability. [1] Although the etiology of this condition is not completely understood, familial and sporadic forms appear to exist. [2, 3, 4, 5, 6] (Also see Caffey Disease Imaging.) Infantile cortical hyperostosis is typically self-limited; no specific treatment exists.

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Pathophysiology

Infantile cortical hyperostosis is an inflammatory process of unclear etiology. In the early stages of this condition, inflammation of the periosteum and adjacent soft tissues is observed. As this resolves, the periosteum remains thickened, and subperiosteal immature lamellar bone is noted. The bone marrow spaces contain vascular fibrous tissue. Mature specimens show hyperplasia of the lamellar cortical bone without inflammation or subperiosteal changes. [4]

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Etiology

Although the etiology of infantile cortical hyperostosis has not been fully elucidated, there is growing evidence of a genetic component. [7, 8]

Various studies have supported the finding that a heterozygous missense mutation (c.3040c→T [p.41014C]) in exon 41 in the type I collagen alpha1 chain gene (COL1A1) is responsible for this disease. [8, 9, 10, 11, 12, 13, 14, 15]  A link to lethal prenatal cortical hyperostosis has also been reported. Authors have noted that this places infantile cortical hyperostosis in the same family as type I collagen-related diseases such as osteogenesis imperfecta I-IV, Ehlers-Danlos syndromes type I and VII, idiopathic osteoporosis, and dermatofibrosarcoma protuberans.

Kitaoka et al conducted a mutation analysis of the COL1A1 and COL1A2 genes and measured bone mineral density in two patients with Caffey disease. [16]  The patients came from two different families. The index patient and two clinically healthy members of that person's family were found to carry the common heterozygous mutation; no mutations of COL1A1 or COL1A2 were identified in the affected members of the second family.

Bone mineral density was normal in adult patients of both families who had had an episode of cortical hyperostosis, regardless of the presence or absence of the p.Arg1014Cys mutation. [16]  The investigators concluded that Caffey disease is genetically heterogeneous and that affected and unaffected adult patients with or without the common COL1A1 mutation have normal bone mineral density.

Some have suggested that transmission may occur via an infectious agent with a long latency period. Other theories have included a primary arterial abnormality and allergic reaction.

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Epidemiology

Infantile cortical hyperostosis has been reported to affect 3 of 1000 infants younger than age 6 months. [17] The disease may be present at birth or shortly thereafter. The familial form tends to have an earlier onset and is present at birth in 24% of cases, with an average age at onset of 6.8 weeks. [3, 18] The average age at onset for the sporadic form of infantile cortical hyperostosis is 9-11 weeks. No race- or sex-based predilection has been established.

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Prognosis

Infantile cortical hyperostosis usually runs its course and resolves without sequelae in 6-9 months. However, the possibility of recurrence should not be ruled out.

Navarre et al reported the case of a 12-year-old female patient who presented with symptoms of pain and swelling of both forearms and legs. [19]  These symptoms were similar to symptoms present at the age of 1 month, at which time she was diagnosed as having cortical hyperostosis. Genetic analysis confirmed the COL1A1 mutation. Radiologic investigation revealed new periosteal bone formation of the right and left ulnae and the left fibula, suggesting a recurrence of cortical hyperostosis.

Navarre et al conducted a review of the literature, using the Medline database between 1948 and 2011, and found that the literature confirms the possibility of recurrence. [19]  They concluded that the diagnosis of recurrent cortical hyperostosis should be considered for patients who experienced cortical hyperostosis in infancy and who present with similar symptoms during adolescence.

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