Infantile cortical hyperostosis and COL1A1 mutation in four generations

Abstract

Infantile cortical hyperostosis (ICH, OMIM 114000) is a rare familial disorder which affects infants. It spontaneously heals in the first years of life. The disease is characterized by regressive subperiosteal hyperosteogenesis mainly affecting long bones, mandible, clavicles, and ribs which are remarkably swollen and deformed on X-rays. But it is also important to take into consideration the autosomal dominant pattern of inheritance to detect it. In 2005 Gensure et al. detected 3040C → T mutation in COL1A1 gene in three unrelated ICH families. Four generations of patients belonging to the same family were examined in our study. Molecular testing has now disclosed a pathogenic mutation in nine of them. The patients spontaneously recovered. Although our paper shows a distinct correlation between R836C mutation and ICH, there is a certain interindividual and intra-familial variability.

Fig. 1

Pedigree of the Italian ICH family. Symbols: arrow, proband; black, affected individuals with COL1A1 mutation; black-gray, heterozygous individual which did not remember ICH data; gray with central black dot, heterozygous asymptomatic; gray, ICH suspected; individuals tested negative are indicated with an horizontal line over their symbol; white, unaffected individuals

Fig. 2

a Patient VI-1 at 14 days old, mandibular deformation. b X-ray of arms. c At 1 year old, bowed arms. d At 3 years old, swelling regression. e At 7 years old, bowed right forearm. f Patient V-5 at 2 months old, swelling of leg. g At 3 years old, full recovery. h Patient VII-2 at 2 months old, X-ray of leg. i, j At 2 years old, light swelling of mandible and leg

Fig. 3

a Representation of COL1A1 gene; the 41 exons are shown as filled boxes and the mutation Arg836Cys related to ICH was also indicated. b Genomic DNA wild type around the site of mutation. c Sequence of a ICH patient with a heterozygous single-nucleotide substitution converting an arginine to cysteine (reference sequence NP_000079.2)