Osteogenesis Imperfecta

Osteogenesis imperfecta, also known as brittle bone disease, is a hereditary genetic disorder characterized by an alteration in collagen formation, leading to abnormal bone fragility, causing frequent fractures and bone deformities. Fractures are more common during childhood and may decrease after the growth phase.

Based on severity, four main types are distinguished:

• Osteogenesis imperfecta type I: The mildest and most common form.
• Osteogenesis imperfecta type II: The most severe type, leading to perinatal and neonatal death.
• Osteogenesis imperfecta type III: Very severe, but not fatal.
• Osteogenesis imperfecta type IV: Variable severity, with a high survival rate, and patients can benefit from treatment.

Symptoms

Symptoms vary depending on the type of disease:

Osteogenesis imperfecta type I:

• Occasional fractures.
• Mild bone deformities: curvature of the tibia and femur.
• Joint hyperlaxity.
• Muscle and joint pain due to hyperlaxity.
• Poor muscle development.
• Blue sclerae: The sclera is abnormally thin, making veins visible.
• Hearing loss.
• Dentinogenesis imperfecta may occur: yellowish or grayish teeth that are brittle and underdeveloped.

Osteogenesis imperfecta type II: Symptoms are evident in the uterus or at birth.

• Extreme bone fragility: skull weakness may prevent the brain from being protected during birth, potentially causing neonatal death.
• Skull and chest fractures during birth or in the uterus.
• Flattened vertebrae.
• Short arms and legs.
• Malformations in the ribs and long bones of the legs.
• Blue sclerae.

Osteogenesis imperfecta type III:

• Short stature.
• Scoliosis: abnormal curvature of the spine.
• Joint hyperlaxity.
• Poor muscle development.
• Frequent fractures due to minor trauma.
• Large skull.
• Triangular-shaped face due to excessive skull growth and underdevelopment of facial bones.
• Chest deformities.
• Blue sclerae that turn white during adolescence.

Osteogenesis imperfecta type IV:

• Short stature.
• Bone deformities.
• Frequent fractures.
• Dentinogenesis imperfecta may occur.
• Hearing loss may be present.

Causes

Osteogenesis imperfecta is caused by a mutation in the genes responsible for producing type I collagen, a key component of bones (providing elasticity and flexibility) and ligaments. The mutation results in deficiencies in either the structure or quantity of collagen, leading to improper bone formation. The defective gene is usually inherited from one or both parents, although, in some cases, the mutation occurs after conception.

Risk Factors

The likelihood of developing the disease depends solely on the presence of the defective gene. Therefore, if one or both parents are carriers, it is highly probable that their child will have osteogenesis imperfecta.

Complications

As mentioned, type II osteogenesis imperfecta is often fatal, whereas the remaining types, with treatment, have a good life expectancy. However, the collagen deficiency that causes osteogenesis imperfecta can lead to severe complications:

• Respiratory problems and pneumonia due to chest wall deformities and lung tissue deficiencies.
• Spinal cord and brainstem damage when the upper spine compresses the base of the skull due to flattening or vertebral malformations.
• Heart problems due to valve dysfunction.
• Muscle atrophy due to prolonged immobilization caused by fractures.
• Permanent deformities.
• Difficulty walking, which may require orthopedic devices, crutches, or wheelchairs.

Prevention

Since osteogenesis imperfecta is congenital, it cannot be prevented. However, if carrying the mutated gene or having a family history, assisted reproductive techniques can help prevent passing the disease to offspring. Preimplantation genetic diagnosis allows the selection of genetically healthy embryos for in vitro fertilization.

Which Doctor Treats Osteogenesis Imperfecta?

Osteogenesis imperfecta is evaluated and treated by specialists in rheumatology and pediatric rheumatology.