Prenatal cortical hyperostosis with COL1A1 gene mutation

Abstract

Infantile cortical hyperostosis (Caffey disease) is benign and self-limiting when it presents near or after birth but it is usually lethal when it presents earlier. We present the clinical, ultrasonic, radiographic, and pathologic findings in an instructive case of early onset prenatal cortical hyperostosis. The pregnancy of a 21-year-old woman was medically terminated at 30 weeks of gestation after a diagnosis of severe osteogenesis imperfecta. Prenatal ultrasounds showed short long bones. Postmortem radiographs showed hyperostosis in long bones, ribs and mandible. The affected skeleton showed marked bony sclerosis and ballooning of the diaphyses of the long bones with periosteal sclerosis. A complete autopsy showed characteristic histologic findings of infantile cortical hyperostosis in affected bones. A missense mutation (3040C --> T) in exon 41 the gene encoding the alpha 1 chain of type I collagen was found in fetus pulmonary tissue. Neither the severe form nor the mild form of prenatal cortical hyperostosis were thought to be related to collagen I mutations. Our study indicates that a heterozygous 3040C --> T mutation can also be found in lethal prenatal cortical hyperostosis.

COL1A1 Mutation in an Indian Child with Caffey Disease

“…The heterozygous mutation in the COL1A1 gene (R1014C) that was found in the present case, has previously been reported in French-Canadian, Australian, Thai and Korean kindred with the classic familial form of the disease [1][2][3][4]. This mutation causes a substitution of arginine by cysteine at position 836 within the helical domain of the α1 chain of type I collagen.…”

“…Both familial and sporadic occurrences have been reported. The familial autosomal dominant form has now been found to be a collagenopathy caused by a single heterozygous missense mutation in COL1A1 (c3040C>T; p R1014C) [1][2][3][4]. Though there are several case reports of Caffey disease from India, no data regarding their genetic mutation pattern have been published.…”

Caffey disease: New perspectives on old questions

“…Subsequently, other groups identified the R836C mutation in Thai, Korean, Indian and Australian kindreds with the classical familial form of the disease and in sporadic cases of the infantile and prenatal forms of disease. Taken together these studies validated the pathogenetic role of this particular amino acid substitution in Caffey disease [21–24]. …”

Infantile cortical hyperostosis and COL1A1 mutation in four generations

“…However, mutational analysis of COL1A1 gene in two fetuses manifesting ICH characteristics disclosed a wild genotype [18]. Kamoun-Goldrat et al [21] reported an ICH fetus terminated at 30 weeks after a diagnosis of severe osteogenesis imperfecta. A postmortem test confirmed ICH.…”