SNP Shot: Genomic Insights

Vitamin D-dependent rickets is a bone development disorder characterized by soft, weak bones (rickets). This condition has several subtypes, primarily distinguished by their genetic origins: type 1A (VDDR1A), type 1B (VDDR1B), and type 2A (VDDR2A). A very rare form, type 2B (VDDR2B), exists, but less is known about it.

Symptoms of vitamin D-dependent rickets usually appear within the first few months of life and are generally similar across all types. Bone pain, delayed growth, and frequent fractures are common. As children with this condition begin to walk, they may develop bowed legs due to bone weakness. Impaired bone development also leads to widening of the metaphyses (areas near the ends of bones where new bone is formed), especially noticeable in the knees, wrists, and ribs. Some individuals may experience dental issues like thin enamel and increased cavities. Hypotonia (poor muscle tone) and muscle weakness are also frequently observed, and some individuals may experience seizures.

Vitamin D-dependent rickets involves imbalances in blood components. A key early sign across all types is hypocalcemia (low calcium levels), which is vital for bone and teeth formation. Individuals also exhibit elevated levels of parathyroid hormone (PTH), leading to secondary hyperparathyroidism. Additionally, hypophosphatemia (low phosphate levels) is present. Vitamin D-dependent rickets types 1 and 2 can be differentiated by calcitriol (active vitamin D) levels; VDDR1A and VDDR1B are associated with low calcitriol, while VDDR2A and VDDR2B are associated with high calcitriol.

Alopecia (hair loss) can occur in VDDR2A, but it's not a universal symptom. Affected individuals may have sparse, patchy, or complete hair loss on their heads, and some may also experience body hair loss.

Inheritance:

Vitamin D-dependent rickets typically follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must have mutations for the condition to manifest. Parents of an individual with an autosomal recessive disorder each carry one mutated gene copy but usually don't exhibit symptoms.

In at least one VDDR1B family, individuals with a single mutated copy of the CYP2R1 gene displayed mild symptoms of vitamin D-dependent rickets, while those with mutations in both copies showed typical signs and symptoms. This inheritance pattern is termed incomplete autosomal dominance.

In rare instances, VDDR2A may be inherited in an autosomal dominant manner. This means that only one altered copy of the VDR gene in each cell is sufficient to cause the condition. In these cases, one of the affected person's parents also has the condition.