Signs & Symptoms of MIOP

  • Pain
  • Frequent, poorly healing fractures
  • Bone infection (osteomyelitis)
  • Dental problems including delayed eruption of teeth and malformed teeth
  • Frontal Bossing of the skull (prominent forehead)


Relate to the brittleness of the bones and the abnormal healing associated with deficient osteoclast formation
  • Compression of the nerves in the skull leading to visual and hearing impairments
  • Headaches
The findings in the skull (frontal bossing, cranial nerve compression, headaches) of patients with osteopetrosis relate to the abnormal bone remodeling. The skull may be abnormally shaped with a prominent forehead, but more concerning is the fact the tunnel through the skull (foramina) through which the cranial nerves travel may become pinched off. Compression of cranial nerves most commonly lead to abnormal eye movements, visual impairments, hearing impairments and facial paralysis. Abnormal remodeling of the skull bones may also lead to an obstruction in the flow of the cerebral-spinal fluid.
  • Enlarged liver and spleen
  • Low blood counts (anemia, low platelets, low white blood cells)
The symptoms of low blood counts and an enlarged liver and spleen reflect the abnormal marrow space. Without osteoclasts to carve the marrow cavity out of dense bone, there is limited room to make blood cells. Bone marrow stem cells are forced to expand in the liver and spleen causing the abdominal organs to dramatically enlarge. In patients with severe forms of osteopetrosis, the liver and spleen are the primary site for bone marrow activity and blood cell formation.
  • Failure to thrive
  • Hypocalcemia (low calcium)
Poor nutrition and poor weight gain is a common symptoms in infants and children with severe illnesses. Symptomatic hypocalcemia (or low blood levels of calcium) results from the constant deposition of minerals in bone without resorption and recycling. Symptoms include muscle cramps and tetany (involuntary muscle contraction). In infants these symptoms may be mistaken for facial ticks or even seizures.


Types of Osteopetrosis

In general terms there are 2 different kinds of osteopetrosis: Autosomal Dominant Osteopetrosis and Autosomal Recessive Osteopetrosis.

Autosomal Dominant Osteopetrosis means that the person inherited a single copy of the abnormal gene from a parent or there was a spontaneous mutation in one copy of the gene. This means that there may be a second functioning gene occasionally resulting in some osteoclast activity and a less severe form of the disease. Patients with Autosomal dominant osteopetrosis may have mild, moderate or severe disease. In most forms, affected patients are diagnosed late in childhood or in adulthood.

Genes involved in autosomal dominant osteopetrosis include:

Type 1 – LRP5
Type 2 – CLCN7

Autosomal Recessive Osteopetrosis means that the person inherited 2 abnormal copies of the gene and have little or no normal osteoclast activity. Autosomal recessive osteopetrosis is also called malignant infantile osteopetrosis (MIOP). Patients with Autosomal recessive osteopetrosis may be fatal without aggressive treatment. Cranial nerve compression, increased spinal fluid pressure, low blood counts, and enlargement of the liver and spleen are common findings at diagnosis. Low calcium may be present at birth and is a clue to the diagnosis of osteopetrosis.

Genes involved in autosomal recessive osteopetrosis include:

Type 1 – TCIRG1
Type 2 – TNFSF11
Type 3 – CA2
Type 4 – CLCN7
Type 5 – OSTM1
Type 6 – PLEKHM1
Type 7 – TNFRSF11A

Other Resources

Clinical Trials: