SNP Shot: Genomic Insights

Caffey disease, also known as infantile cortical hyperostosis, is a rare bone disease primarily affecting infants. Its hallmark is excessive formation of new bone, called hyperostosis. The most commonly affected bones include the jawbone, shoulder blades (scapulae), collarbones (clavicles), and the long, central parts (diaphyses) of the long bones in the arms and legs. X-rays may reveal that these bones are significantly thickened, sometimes doubling or tripling in width. In certain instances, adjacent bones, like ribs or the paired bones in the forearms (radius and ulna) or lower legs (tibia and fibula), may fuse together. Infants with Caffey disease often exhibit swelling of joints and soft tissues, such as muscles, accompanied by pain and redness in the affected areas. Fever and irritability are also common symptoms.

The symptoms of Caffey disease typically manifest before an infant reaches 5 months of age. In rare situations, ultrasound imaging can detect skeletal abnormalities during the final weeks of prenatal development. A more severe and often fatal condition, known as lethal prenatal cortical hyperostosis (sometimes called lethal prenatal Caffey disease), appears earlier in development; however, it's generally considered a distinct condition.

The swelling and pain associated with Caffey disease typically resolve spontaneously within a few months, for reasons that are not fully understood. Through bone remodeling, a natural process where old bone is replaced by new bone, the excessive bone is usually reabsorbed by the body, becoming undetectable on x-rays by the age of 2. However, if adjacent bones have fused, this fusion may persist, potentially leading to complications. For example, fused ribs can cause scoliosis (curvature of the spine) or restrict chest expansion, leading to breathing difficulties.

Most individuals with Caffey disease experience no further related issues after early childhood. Occasionally, a recurrence of hyperostosis may occur years later. Furthermore, some adults who had Caffey disease as infants may develop other bone and connective tissue abnormalities. Connective tissues provide strength and flexibility throughout the body. These adults may exhibit loose joints (joint laxity), unusually stretchy (hyperextensible) skin, or a predisposition to hernias (protrusion of organs through muscle gaps).

Inheritance:

The inheritance pattern is autosomal dominant, meaning that usually only one copy of the mutated gene in each cell is sufficient to cause the disorder. Interestingly, about 20% of individuals carrying the Caffey disease gene mutation don't show any signs or symptoms, a phenomenon known as incomplete penetrance. In some cases, the mutation is inherited from an affected parent. In other instances, the mutation arises spontaneously in the affected individual, with no family history of the disorder.