Osteopetrosis is characterized by overly dense bones throughout the body. Symptoms include fractures, low blood cell production, and loss of cranial nerve function causing blindness, deafness, and/or facial nerve paralysis. Affected individuals may experience Frequent infections of teeth and the bone in the jaw.
Osteopetrosis, Autosomal Recessive; Malignant Infantile Type The most severe type of osteopetrosis, malignant infantile type, is apparent from birth, and if left untreated, can lead to death in the first decade of life. Symptoms vary depending on the exact gene change (mutation). Affected individuals may have an abnormally large head (macrocephaly). They may also have hydrocephalus, characterized by inhibition of the normal flow of cerebrospinal fluid (CSF) within and abnormal widening (dilatation) of the cerebral spaces of the brain (ventricles), causing accumulation of CSF in the skull and potentially increased pressure on brain tissue. Symptoms that affect the eyes may include wasting away (atrophy) of the retina, eyes that appear widely spaced (hypertelorism), eyes that protrude from their orbits (exophthalmos), cross-eyes (strabismus), involuntary rhythmic movements of the eyes (nystagmus), and blindness.
Other symptoms associated with malignant infantile type of osteopetrosis include hearing loss, abnormally Small jaw (micrognathia), chronic Inflammation of the mucous membranes in the nose (rhinitis), Eating difficulties and/or growth retardation. Some affected individuals experience delays in acquiring skills that require the coordination of muscles and voluntary movements (delayed psychomotor development). Some affected individuals may experience delayed tooth development or severe dental caries. In addition, abnormal enlargement of the liver and spleen (hepatosplenomegaly); abnormal hardening of some bones (osteosclerosis); fractures, usually of the ribs and long bones; Inflammation of the lumbar vertebrae (osteomyelitis); increased density of the cranial bones (cranial hyperostosis) leading to nerve compression; and/or increased pressure inside the skull may also occur. Patients can also present with Seizures due to low levels of calcium in the blood. Symptoms of severe neurodegeneration can manifest in rare variants of malignant infantile osteopetrosis.
Some affected individuals with the malignant infantile type of osteopetrosis may also experience consequences of reduced bone marrow space: marked deficiency of all types of blood cells (pancytopenia), the formation and development of blood cells outside the bone marrow, as in the spleen and liver (extramedullary hematopoiesis), and the occurrence of myeloid tissue in extramedullary sites (myeloid metaplasia). This may lead to Frequent infections such as pneumonia and urinary tract infections. Affected individuals may also experience low levels of iron in red blood cells (anemia), due to both reduced bone marrow space and increased destruction of red blood cells due to an enlarged spleen. Of note, hematological defects usually present before neurological ones.
Osteopetrosis, Autosomal Dominant; Adult Type A milder form of osteopetrosis, the adult type, is usually diagnosed in late childhood or adulthood. There is predominance of bone symptoms, including osteosclerosis, fractures after minimal trauma (usually of the ribs and long bones), osteomyelitis (especially of the jaw) and cranial hyperostosis. In some cases, affected individuals may have pus-filled sacs in the tissue around the teeth (dental abscess). In many cases, individuals may exhibit no symptoms (asymptomatic).
Affected individuals may also experience rhinitis, hepatosplenomegaly, anemia and extramedullary hematopoiesis.
Osteopetrosis, Intermediate Autosomal Recessive The intermediate type is usually found in children and can be inherited as a autosomal recessive or autosomal dominant trait. The severity of the disease is variable. Symptoms may include abnormal hardening of some bones; fractures; osteomyelitis especially of the mandible, knees that are abnormally close together and ankles that are abnormally wide apart (genu valgum) and cranial hyperostosis.
Symptoms of the intermediate type of osteopetrosis may also include gradual deterioration of the nerves of the eyes (optic atrophy), loss of vision, muscular weakness, and rhinitis. Some affected individuals may experience abnormal protrusion of the lower jaw (mandibular prognathism), dental anomalies, baby teeth that do not fall out (deciduous retention), tooth crown malformation, dental caries, and facial paralysis. Other symptoms include hepatosplenomegaly, anemia, decreased levels of circulating blood platelets (thrombocytopenia), pancytopenia, and extramedullary hematopoiesis.
Osteopetrosis: X-linked Recessive X-linked osteopetrosis is extremely rare but severe, with only a few cases reported worldwide. In addition to classical symptoms linked with osteopetrosis, it is associated with immunodeficiency, localized fluid retention and tissue Swelling (lymphedema) as well as abnormalities of the hair, skin, nails and sweat glands (ectodermal dysplasia).