Background
In 1945, Caffey first described infantile cortical hyperostosis (Caffey disease), as shown in the image below, 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 the eMedicine article Caffey Disease, in Radiology.)
Radiograph from a 5-month-old infant with infantile cortical hyperostosis. This image depicts cortical thickening in the pelvis secondary to the disease. Recent studies
A number of 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 infantile cortical hyperostosis. A link to lethal prenatal cortical hyperostosis has also been reported. Studies have noted that this places Caffey disease 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.[7, 8, 9, 10, 11, 12]
The effects of Caffey disease can sometimes resemble those of child physical abuse. A case study by Al Kaissi et al showed that accurate diagnosis of the cause of unexplained trauma or fractures in children requires that clinicians be familiar with such diseases and demonstrated the importance of well-interpreted imaging studies in these diagnoses. The authors reported on a case of suspected child abuse, a female infant aged 3 months with multiple inflamed swellings over the limbs. Imaging studies revealed features that were consistent with Caffey disease, including massive sclerosis of the skull bone associated with significant cortical hyperostosis, as well as mandibular enlargement secondary to new cortical bone formation. Characteristic features of Caffey disease were also seen in the patient's radius and tibia.[13]
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]
Epidemiology
Frequency
United States
The disease has been reported to affect 3 per 1000 infants younger than age 6 months.[14]
Mortality/Morbidity
Infantile cortical hyperostosis is a self-limited condition.
Race
No racial predilection has been established.
Sex
No sex predilection has been established.
Age
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, 15] The average age at onset for the sporadic form of infantile cortical hyperostosis is 9-11 weeks.
Caffey J. Infantile cortical hyperostoses. J Pediatr. 1946;29:541-59.
Bernstein RM, Zaleske DJ. Familial aspects of Caffey's disease. Am J Orthop. Oct 1995;24(10):777-81. [Medline].
Saul RA, Lee WH, Stevenson RE. Caffey's disease revisited. Further evidence for autosomal dominant inheritance with incomplete penetrance. Am J Dis Child. Jan 1982;136(1):55-60. [Medline].
Kamoun-Goldrat A, le Merrer M. Infantile cortical hyperostosis (Caffey disease): a review. J Oral Maxillofac Surg. Oct 2008;66(10):2145-50. [Medline].
Wong YK, Cheng JC. Infantile cortical hyperostosis of the mandible. Br J Oral Maxillofac Surg. Sep 2008;46(6):497-8. [Medline].
Skiker I, Dafiri R. [Unusual lytic bone lesions in Caffey's disease]. J Radiol. Nov 2008;89(11 Pt 1):1767-9. [Medline].
Kamoun-Goldrat A, Martinovic J, Saada J, Sonigo-Cohen P, Razavi F, Munnich A, et al. Prenatal cortical hyperostosis with COL1A1 gene mutation. Am J Med Genet A. Jul 15 2008;146A(14):1820-4. [Medline].
Kroon ND, Smith F, Sanghavi R, Sarkar P. Prenatal cortical hyperostosis (Caffey disease) with Down syndrome. J Obstet Gynaecol. Jan 2009;29(1):57-8. [Medline].
Cho TJ, Moon HJ, Cho DY, Park MS, Lee DY, Yoo WJ. The c.3040C > T mutation in COL1A1 is recurrent in Korean patients with infantile cortical hyperostosis (Caffey disease). J Hum Genet. 2008;53(10):947-9. [Medline].
Suphapeetiporn K, Tongkobpetch S, Mahayosnond A, Shotelersuk V. Expanding the phenotypic spectrum of Caffey disease. Clin Genet. Mar 2007;71(3):280-4. [Medline].
Gensure RC, Mäkitie O, Barclay C, Chan C, Depalma SR, Bastepe M. A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. J Clin Invest. May 2005;115(5):1250-7. [Medline].
Glorieux FH. Caffey disease: an unlikely collagenopathy. J Clin Invest. May 2005;115(5):1142-4. [Medline].
Al Kaissi A, Petje G, De Brauwer V, Grill F, Klaushofer K. Professional awareness is needed to distinguish between child physical abuse from other disorders that can mimic signs of abuse (Skull base sclerosis in infant manifesting features of infantile cortical hyperostosis): a case report and review of the literature. Cases J. Feb 9 2009;2(1):133. [Medline].
Herring JA, ed. Infantile cortical hyperostosis. Tachdjian's Pediatric Orthopaedics. 3rd ed. Philadelphia, Pa: WB Saunders Co; 2002:1561-5.
Shannon FJ, Murphy M, Atchia I, Phelan E, Fogarty EE. Caffey's disease: an unusual cause for concern. Ir J Med Sci. Jun 2007;176(2):133-6. [Medline].
Kovacic K, Hajnzic TF, Roncevic S, et al. Mandibular Caffey's disease--case report. Coll Antropol. Mar 2007;31(1):359-61. [Medline].
Suphapeetiporn K, Tongkobpetch S, Mahayosnond A, Shotelersuk V. Expanding the phenotypic spectrum of Caffey disease. Clin Genet. Mar 2007;71(3):280-4. [Medline].
Blank E. Recurrent Caffey's cortical hyperostosis and persistent deformity. Pediatrics. Jun 1975;55(6):856-60. [Medline].
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