What is BPAN?

Beta-propeller protein associated neurodegeneration (BPAN) is a spontaneous and rare genetic mutation that damages the brain and nervous system, causing delays and defects in normal child development, speech, and motor skills.  Seizure disorders are commonly associated.  It is a progressive disease, eventually leading to loss of brain function, dementia, paralysis, and premature death in early adulthood.

BPAN is caused by a genetic mutation in a gene called WDR-45 that is located on the X- chromosome.  It is a typically a random mutation that is not inherited from the parents.  The actual defect in the WDR-45 gene is variable, thus affected individuals may have differences in the severity of brain degeneration.

Females are most often affected, because X-chromosome defects are usually lethal to males before they are born.  BPAN is a very rare disease, as there are only approximately 500 known cases worldwide.  The actual number may be much higher – diagnosis of BPAN requires examination of the entire genome (all of a person’s DNA).  This testing is expensive, time consuming, and only available at specialized laboratories.  Many children with developmental delay and seizure disorders do not have access to such sophisticated health care, and diseases such as BPAN may go undetected.

Developmental delay and early-onset seizures are typical presenting signs of BPAN.  Seizures can be of any type – fever-induced, partial seizures, or grand-mal (severe) seizures.  They may be frequent (multiple seizures per day) or infrequent (1 or 2 per year).

Intellectual disability and limited ability to speak are hallmarks of BPAN.  Affected children have cognitive defects (difficulty in thinking, understanding, and learning).  They also have defects in expressive speech, with limited vocabularies and difficulty in sentence formation.  First words may not come until age 2 or 3.  A total of only 30-50 words in mid childhood is typical, and many words are unintelligible or garbled.

Poor motor skills are another effect of BPAN.  Children display slow and incomplete development in walking, running, and handling objects.  Skills such as dressing, washing hands, and eating with utensils are difficult.  Falling can be frequent.

The outlook for children with BPAN is dire.  BPAN causes neuronal cell loss (death of brain cells).  As they grow to adolescence and early adulthood, the loss of brain cells leads to dementia and parkinsonism (loss of muscle function and coordination).  Lifespan after that may vary, but the quality of that life will be minimal.

The hope of affected families is that a way to replace or correct the mutated WDR-45 gene can be found. This way, BPAN can be stopped before children reach their teenage years, preventing irreversible brain loss, dementia, and a premature death.