Caffey disease

Alternate names

Infantile cortical hyperostosis

Definition

Caffey disease is a bone disorder that most often occurs in babies. It is characterized by the excessive formation of new bone (hyperostosis) in the jaw, shoulder blades, collarbones, and shafts of long bones in the arms and legs.

Epidemiology

Caffey disease has been estimated to occur in approximately 3 per 1,000 infants worldwide. A few hundred cases have been described in the medical literature. Researchers believe this condition is probably underdiagnosed because it usually goes away by itself in early childhood.

Cause

• A mutation in the COL1A1 gene causes Caffey disease.
• The COL1A1 gene provides instructions for making part of a large molecule called type I collagen.
• Collagens are a family of proteins that strengthen and support many tissues in the body, including cartilage, bone, tendon, and skin.
• In these tissues, type I collagen is found in the spaces around cells.
• The collagen molecules are cross-linked in long, thin, fibrils that are very strong and flexible.
• Type I collagen is the most abundant form of collagen in the human body.

Gene mutations

• The COL1A1 gene mutation that causes Caffey disease replaces the protein building block (amino acid) arginine with the amino acid cysteine at protein position 836 (written as Arg836Cys or R836C).
• This mutation results in the production of type I collagen fibrils that are variable in size and shape, but it is unknown how these changes lead to the signs and symptoms of Caffey disease.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

• This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is usually sufficient to cause the disorder. About 20 percent of people who have the mutation that causes Caffey disease do not experience its signs or symptoms; this phenomenon is called incomplete penetrance.
• In some cases, an affected person inherits the mutation that causes Caffey disease from a parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Onset

The signs and symptoms of Caffey disease are usually apparent by the time an infant is 5 months old. In rare cases, skeletal abnormalities can be detected by ultrasound during the late stages of pregnancy.

Signs and symptoms

• Caffey disease is characterized by excessive new bone formation (hyperostosis).
• The bone abnormalities mainly affect the jawbone, shoulder blades, collarbones, and the shafts of long bones in the arms and legs.
• Affected bones may double or triple in width. In some cases, two bones in the forearms or lower legs become fused together.
• Babies with this condition may also develop swelling of joints and soft tissues with pain and redness in the affected areas.
• They may also be feverish and irritable.
• For unknown reasons, the swelling and pain associated with Caffey disease tend to go away within a few months.
• The excess bone also disappears as it is reabsorbed by the body through a normal process called bone remodeling.
• If two bones have been fused, they may remain that way, which can lead to complications such as scoliosis and breathing problems.
• Most people with Caffey syndrome have no further problems related to the disorder after early childhood.
• Occasionally, another episode of hyperostosis occurs years later. In addition, some adults who had Caffey disease have other abnormalities of the bones and connective tissues, including loose joints, stretchy skin or hernias.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Cellulitis(Bacterial infection of skin)
• Cortical irregularity

30%-79% of people have these symptoms

• Behavioral abnormality(Behavioral changes)
• Fever
• Hyperesthesia
• Periosteal thickening of long tubular bones

5%-29% of people have these symptoms

• Calvarial hyperostosis(Overgrowth of skullcap)
• Cortical thickening of long bone diaphyses
• Facial asymmetry(Asymmetry of face)
• Feeding difficulties in infancy
• Increased circulating antibody level
• Proptosis(Bulging eye)
• Respiratory insufficiency(Respiratory impairment)
• Scoliosis

Diagnosis

Caffey disease should be suspected in individuals with the following:

• Clinical findings of irritability, fever, and/or pallor accompanied by soft-tissue swelling and pain adjacent to involved bones
• Radiologic findings of subperiosteal cortical hyperostosis of the diaphyses of the long bones (with sparing of the epiphyses), as well as the ribs, scapulae, clavicles, and mandible
• Findings typically appearing between birth and age five months and resolving spontaneously by age two years, although recurrence in adolescence is possible

The diagnosis of Caffey disease is established in a proband with typical clinical and radiographic findings and a heterozygous pathogenic variant in COL1A1 identified by molecular genetic testing..

Treatment

• Anti-inflammatory agents, antipyretics, and analgesics can be used in the short term to decrease swelling and fever and to relieve pain
• No recommendations for the prevention of recurrence of hyperostosis currently exist.[1].

NIH genetic and rare disease info

• NIH info on Caffey disease

Caffey disease is a rare disease.

Caffey disease Resources
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