Osteoporosis-Pseudoglioma Syndrome
Patient Information
Characteristics
Background and History
This oddly-named disorder has primary manifestations in bone and the eye.
Clinical Correlations
Infants have a growing mass of abnormal tissue in the eye which often causes hemorrhages that lead to retinal detachments. Blindness is often the result as early as infancy or before adulthood. The retina never develops normally. Cataracts and glaucoma may also occur. A few individuals have been described as having mental delays but others have normal intelligence. There may be some muscle weakness and infants are sometimes described as floppy.
Bones also do not form normally and are fragile due to lack of density. Fractures are common. Scoliosis, deformed limbs, and short stature may result. On X-ray, they appear delicate and osteoporotic.
Genetics
Inheritance
The gene mutation responsible seems to cause disease in the presence of both a single or double mutation. This disorder therefore can be inherited both in an autosomal dominant and an autosomal recessive pattern but it generally appears in a horizontal pattern suggestive of autosomal recessive inheritance.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
Diagnosis and Prognosis
This condition requires ophthalmologic, pediatric, and orthopedic collaboration for diagnosis. Orthopedic repair is indicated for fractures and scoliosis. Some improvement in bone density may follow bisphosphonate drug treatment if begun early. There is no treatment that prevents blindness.
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