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Autosomal dominant osteopetrosis 2(OPTA2)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Albers-Schoenberg disease; Albers-Schonberg disease; ALBERS-SCHONBERG DISEASE, AUTOSOMAL DOMINANT; Albers-Schönberg osteopetrosis; Autosomal Dominant Osteopetrosis Type II; Marble bones; MARBLE BONES, AUTOSOMAL DOMINANT; Osteopetroses; Osteosclerosis fragilis; OSTEOSCLEROSIS FRAGILIS GENERALISATA
SNOMED CT: Autosomal dominant osteopetrosis type 2 (725050005); Albers Schonberg osteopetrosis (725050005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Gene (location): CLCN7 (16p13.3)
Monarch Initiative: MONDO:0008156
OMIM®: 166600
Orphanet: ORPHA53

Disease characteristics

Excerpted from the GeneReview: CLCN7-Related Osteopetrosis
The spectrum of CLCN7-related osteopetrosis includes infantile malignant CLCN7-related autosomal recessive osteopetrosis (ARO), intermediate autosomal osteopetrosis (IAO), and autosomal dominant osteopetrosis type II (ADOII; Albers-Schönberg disease). ARO. Onset is at birth. Findings may include: fractures; reduced growth; sclerosis of the skull base (with or without choanal stenosis or hydrocephalus) resulting in optic nerve compression, facial palsy, and hearing loss; absence of the bone marrow cavity resulting in severe anemia and thrombocytopenia; dental abnormalities, odontomas, and risk for mandibular osteomyelitis; and hypocalcemia with tetanic seizures and secondary hyperparathyroidism. Without treatment maximal life span in ARO is ten years. IAO. Onset is in childhood. Findings may include: fractures after minor trauma, characteristic skeletal radiographic changes found incidentally, mild anemia, and occasional visual impairment secondary to optic nerve compression. Life expectancy in IAO is usually normal. ADOII. Onset is usually late childhood or adolescence. Findings may include: fractures (in any long bone and/or the posterior arch of a vertebra), scoliosis, hip osteoarthritis, and osteomyelitis of the mandible or septic osteitis or osteoarthritis elsewhere. Cranial nerve compression is rare. [from GeneReviews]
Cristina Sobacchi  |  Anna Villa  |  Ansgar Schulz, et. al.   view full author information

Additional descriptions

Autosomal dominant osteopetrosis-2 (OPTA2) is characterized by segmentary osteosclerosis, predominantly at the vertebral endplates ('rugger-jersey spine'), iliac wings ('bone within bone' sign), and skull base. Clinical manifestations include cranial nerve palsies, mandibular osteomyelitis, osteoarthritis of the hip, and nontraumatic fractures, particularly of the long bones (Cleiren et al., 2001). OPTA2 accounts for 70% of cases of autosomal dominant osteopetrosis (Del Fattore et al., 2008). For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (607634).  http://www.omim.org/entry/166600
From MedlinePlus Genetics
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.

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.

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. 

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 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.

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).  https://medlineplus.gov/genetics/condition/osteopetrosis

Clinical features

From HPO
Bone marrow hypocellularity
MedGen UID:
Concept ID:
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Facial paralysis
MedGen UID:
Concept ID:
Disease or Syndrome
Complete loss of ability to move facial muscles innervated by the facial nerve (i.e., the seventh cranial nerve).
Recurrent fractures
MedGen UID:
Concept ID:
Injury or Poisoning
The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture).
Osteoarthritis, hip
MedGen UID:
Concept ID:
Disease or Syndrome
Osteoarthritis of the hip joint.
MedGen UID:
Concept ID:
Abnormally increased formation of dense trabecular bone tissue. Despite the increased density of bone tissue, osteopetrotic bones tend to be more fracture-prone than normal.
Facial palsy
MedGen UID:
Concept ID:
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Generalized osteosclerosis
MedGen UID:
Concept ID:
An abnormal increase of bone mineral density with generalized involvement of the skeleton.
Abnormal pelvic girdle bone morphology
MedGen UID:
Concept ID:
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Abnormality of the vertebral endplates
MedGen UID:
Concept ID:
Anatomical Abnormality
Any abnormality of the vertebral end plates, which are the top and bottom portions of the vertebral bodies that interface with the vertebral disks.
Mandibular osteomyelitis
MedGen UID:
Concept ID:
Disease or Syndrome
Osteomyelitis of the lower jaw.
Visual loss
MedGen UID:
Concept ID:
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).
Elevated serum acid phosphatase
MedGen UID:
Concept ID:

Term Hierarchy

Professional guidelines


Teti A, Econs MJ
Bone 2017 Sep;102:50-59. Epub 2017 Feb 4 doi: 10.1016/j.bone.2017.02.002. PMID: 28167345
Kawai T, Nishikomori R, Heike T
Allergol Int 2012 Jun;61(2):207-17. doi: 10.2332/allergolint.12-RAI-0446. PMID: 22635013

Recent clinical studies


Deng H, He D, Rong P, Xu H, Yuan L, Li L, Lu Q, Guo Y
Mol Pain 2016;12 Epub 2016 Jun 20 doi: 10.1177/1744806916652628. PMID: 27325559Free PMC Article


Deng H, He D, Rong P, Xu H, Yuan L, Li L, Lu Q, Guo Y
Mol Pain 2016;12 Epub 2016 Jun 20 doi: 10.1177/1744806916652628. PMID: 27325559Free PMC Article

Clinical prediction guides

Deng H, He D, Rong P, Xu H, Yuan L, Li L, Lu Q, Guo Y
Mol Pain 2016;12 Epub 2016 Jun 20 doi: 10.1177/1744806916652628. PMID: 27325559Free PMC Article

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