Of the 10 forms of NBIA currently identified, most are recessive. Because most of our genes exist in pairs (one from the mother and one from the father), we normally carry two working copies of each gene. When one copy of a recessive gene has a change (mutation) in it, the person should still have normal health. That person is called a carrier. Recessive diseases only occur when both parents are carriers for the same condition and then pass their changed genes on to their child.
Statistically, the chances are one in four that two carriers would have an affected child, two in four that they would have a child who is also a carrier and one in four that they would have a child without the genetic mutation.
Neuroferritinopathy is a dominant condition. In this case, a person affected with neuroferritinopathy has one working copy of the gene and one copy that has a change, or mutation. This single mutation is enough to cause the disease. There is a one in two chance, or 50 percent, that an affected individual will pass the gene change on to any of his or her children. For neuroferritinopathy, most affected individuals have one parent who is also affected.
Beta-propeller Protein-Associated Neurodegeneration is inherited in an X-linked dominant manner, meaning that a single copy of the mutated gene is enough to cause disease in both males and females. Most affected individuals identified so far have been simplex, or isolated cases; they are the only person in their family to have the disease. The majority are females, indicating the mutations are new, or de novo, and suggesting that mutations may be lethal in most males before birth. Still, parental testing is recommended since recurrence has been reported. If neither parent has the variant, then recurrence is slightly greater than the population risk but still less than one percent. When a parent has the same WDR45 variant and evidence for mosaicism, then the recurrence chance could increase to 50%.
Mitochondrial-membrane Protein-Associated Neurodegeneration (MPAN) is inherited in an autosomal recessive manner and less commonly, in an autosomal dominant manner.
Affected Population: Overall, NBIA affects males and females in equal numbers (BPAN occurs more frequently in females). The frequency of NBIA in the general population is estimated between 1-3/1,000,000 individuals. Because rare disorders like NBIA often go unrecognized, these disorders may be underdiagnosed or misdiagnosed, making it difficult to determine the accuracy of these estimates.
