SNP Shot: Genomic Insights

Osteopetrosis is a bone condition characterized by abnormally dense and compact bone tissue, which is also prone to fractures. Researchers have identified several types of osteopetrosis, generally classified by their inheritance pattern: autosomal dominant or autosomal recessive. These types also vary in the severity of their symptoms.

Autosomal dominant osteopetrosis (ADO), also known as Albers-Schönberg disease, is usually the mildest form. Some individuals with ADO may not experience any symptoms. In these cases, the dense bones might be discovered incidentally during an X-ray performed for another reason.

For those with ADO who do develop symptoms, common features include multiple bone fractures after minor injuries, scoliosis or other spinal issues, hip arthritis, and osteomyelitis (bone infection). These issues typically become apparent in late childhood or adolescence.

Autosomal recessive osteopetrosis (ARO) is a more severe form that manifests in early infancy. Individuals with ARO face a heightened risk of fractures, even from minor bumps and falls. The abnormally dense skull bones can compress cranial nerves, often leading to vision loss, hearing loss, and facial paralysis. The dense bones can also hinder bone marrow function, impairing the production of blood and immune cells. Consequently, individuals with severe osteopetrosis are susceptible to abnormal bleeding, anemia, and recurring infections. In the most critical cases, these bone marrow complications can be fatal during infancy or early childhood.

Other potential features of autosomal recessive osteopetrosis include slowed growth and short stature, dental problems, and hepatosplenomegaly (enlarged liver and spleen). Depending on the specific genetic mutations, individuals with severe osteopetrosis may also exhibit brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).

A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can be inherited in either an autosomal dominant or autosomal recessive manner. The signs and symptoms of IAO, including increased risk of fractures and anemia, become noticeable during childhood. Life-threatening bone marrow problems are generally not present in this form. However, some individuals with IAO have experienced brain calcifications, intellectual disability, and renal tubular acidosis (a kidney disease).

Inheritance:

Osteopetrosis can be inherited in several ways. Autosomal dominant inheritance is the most common pattern, meaning that only one copy of a mutated gene in each cell is enough to cause the condition. Most individuals with autosomal dominant osteopetrosis inherit the condition from a parent who also has it.

Osteopetrosis can also be inherited in an autosomal recessive pattern. This requires both copies of a gene in each cell to have mutations. The parents of someone with an autosomal recessive condition each carry one copy of the mutated gene, but usually do not show any signs or symptoms of the condition themselves.