SNP Shot: Genomic Insights

Hypophosphatasia is a genetic condition impacting bone and tooth development. It disrupts mineralization, a process where minerals like calcium and phosphorus are deposited into developing bones and teeth. Mineralization is essential for creating strong, rigid bones and teeth capable of withstanding chewing.

The symptoms of hypophosphatasia vary greatly in severity and onset, ranging from before birth to adulthood. The most serious cases typically present before birth or in early infancy. Hypophosphatasia weakens and softens bones, leading to skeletal deformities similar to rickets. Infants may be born with short limbs, an unusually shaped chest, and soft skull bones. Additional complications for infants include difficulty feeding and failure to thrive, breathing difficulties, and elevated calcium levels in the blood (hypercalcemia), which can cause repeated vomiting and kidney problems. In some instances, these complications can be life-threatening.

Hypophosphatasia appearing in childhood or adulthood is generally less severe than the infantile form. Early loss of baby teeth is often an initial sign in children. Affected children might experience short stature with bowed legs or knock knees, enlarged wrists and ankles, and an irregular skull shape. Adult hypophosphatasia is characterized by osteomalacia, a softening of the bones. Recurrent fractures in the feet and thigh bones can cause chronic pain. Adults may also experience premature loss of permanent teeth and are more susceptible to joint pain and inflammation.

Odontohypophosphatasia, the mildest form, solely affects the teeth. Individuals with this condition usually have abnormal tooth development and premature tooth loss, but do not exhibit the skeletal abnormalities associated with other forms of hypophosphatasia.

Inheritance:

Severe, early-onset hypophosphatasia follows an autosomal recessive inheritance pattern. This means that both copies of a specific gene in each cell must be altered for the condition to manifest. Typically, parents of a child with an autosomal recessive disorder each carry one altered gene copy but do not exhibit symptoms themselves. Less severe forms of hypophosphatasia can be inherited in either an autosomal recessive or an autosomal dominant manner. Autosomal dominant inheritance means that only one copy of the altered gene in each cell is enough to cause the disorder.