MedGen

A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.

Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).

Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.

In individuals with ADO who develop signs and symptoms, the major features of the condition include multiple bone fractures after minor injury, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.

Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In affected people with no symptoms, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. 

Osteopetrosis is a bone disease that makes bone tissue abnormally compact and dense and also prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant or autosomal recessive. The different types of the disorder can also be distinguished by the severity of their signs and symptoms. [from MedlinePlus Genetics]

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare condition characterized by distinctive radiographic changes, including osteosclerosis localized predominantly to the metaphyses of the long bones. The shafts of the long bones are osteopenic. Laboratory abnormalities include elevated alkaline phosphatase levels in some, but not all, patients. Elevated urinary pyridinoline and deoxypyridinoline levels, markers of osteoclastic activity, have also been reported (Nishimura and Kozlowski, 1993; Kasapkara et al., 2013; Guo et al., 2017). Patients with OSMD have been described who also show hypotonia, developmental delay, seizures, and later-onset spastic paraplegia; however, OSMD resulting from mutation in the LRRK1 gene does not appear to include these neurologic features (Nishimura and Kozlowski, 1993; Kasapkara et al., 2013; Guo et al., 2017). Reviews Howaldt et al. (2020) reviewed published reports of LRRK1-associated OSMD, and noted that patients typically present with recurrent pathologic fractures and osteosclerosis at multiple skeletal sites, predominantly at the metaphyses and vertebral bodies. Variable degrees of osteosclerosis of ribs and skull and of Erlenmeyer flask deformity of the femurs have been observed. [from OMIM]

Dense radiopaque bands of bone which are thicker than the adjacent diaphyseal cortex and may form at the metaphysis of growing bones. They appear on radiographs as bone that is more radiopaque that the adjacent diaphyseal cortex. [from HPO]