1. Osteogenesis Imperfecta (OI)
Affecting the connective tissue by extremely fragile bones that break or fracture easily (brittle bones) without cause.
The severity of OI also varies greatly, even among individuals of the same family.
Four main types of OI have been identified. OI type I is the most
common and the mildest form of the disorder.
( Type II is the most severe )
In most cases are inherited as autosomal dominant traits.

2. Signs & Symptoms : •Blue sclerae •Triangular facies •Macrocephaly
•Hearing loss
•Defective dentition
•Barrel chest
•Scoliosis
•Limb deformities
•Fractures
•Joint laxity
•Growth retardation

3. Osteogenesis Type I
The most common and usually the mildest form of OI. In most cases
Multiple bone fractures usually occurring during childhood through puberty.
Fractures usually begin when an affected child begins to walk
Repeated fractures may result in slight malformation of the bones of the arms and legs (e.g., bowing of the tibia and femur).
Bluish discoloration of the whites of the eyes (blue sclera).
Hearing impairment (i.e., conductive and/or sensorineural hearing loss).
Triangular facial appearance and an abnormally large head (macrocephaly).
Short stature & approximately 20 percent of adults with scoliosis or kyphosis.
Dental abnormalities.

4. Osteogenesis Type II The most severe type
Life-threatening complications at, or shortly after, birth.
Low birth weight, abnormally short arms and legs (limbs), and bluish discoloration of the whites of the eyes (blue sclera)
Extremely fragile bones and numerous fractures present at birth. The ribs and long bones of the legs of affected infants are often malformed.
Underdeveloped lungs and an abnormally small upper chest (thorax) that may result in life-threatening respiratory insufficiency.
Congestive heart failure
A small, narrow nose; a small jaw (micrognathia); and an abnormally soft top of the skull (calvaria) with abnormally large soft spots (large fonatanelle).

5. Osteogenesis Type III
Extremely fragile bones, multiple fractures, and malformed bones.
Multiple fractures are often present at birth. Fractures and malformation of various bones (most often the ribs and long bones) may become worse (progressive malformation) as affected infants and children age.
Progressive malformation of various bones may result in short stature, sideways and front-to-back curvature of the spine (scoliosis and kyphosis
Pulmonary insufficiency and respiratory problems
Progressive bone malformation may result in affected individuals requiring wheelchairs.
Affected infants may have a triangular facial appearance due to an abnormally prominent forehead (frontal bossing) and an abnormally small jaw (micrognathia).
Hearing impairment and brittle, discolored teeth (dentinogenesis imperfecta.

6. Osteogenesis Type IV : Fractures are more common before puberty
Mild to moderate bone malformation and are usually shorter than average
Scoliosis and kyphosis
Triangular facial appearance
Whites of the eyes (sclera) are normal or pale blue during infancy
The pale blue discoloration of the sclera fades
Hearing impairment and brittle, discolored teeth (dentinogenesis imperfecta)

7. Causes :
Types I, II, and IV are inherited as autosomal dominant traits. Most cases of OI
Type II occur without a previous family history of the disorder, resulting instead from a spontaneous genetic change (i.e., new mutation). The inheritance of this mutation is autosomal dominant.
Disruption or changes (mutations) of one of two genes (COL1A1 or COL1A2).
Rare subgroups of OI types II and III may be inherited as autosomal recessive genetic traits.

8. Causes :
In 2006, researchers at the National Institutes of Health (NIH) discovered that a previously unexplained fatal form of osteogenesis imperfecta results from a genetic defect in a different gene known as CRTAP.
The discovery of this gene was described in an article published in the December 28, 2006, New England Journal of Medicine.

9. Affected Populations :
Males and females in equal numbers.
OI type I is estimated to occur in one in 30,000 live births.
OI type II is estimated to occur in one in 60,000 live births.
The overall prevalence of all types of OI is estimated at .5 per 10,000 individuals in the United States.
Approximately 20,000 to 50,000 individuals in the United States have OI.

10. Related Disorders :
Achondroplasia is an inherited disorder characterized by abnormally short arms and legs and short stature (short-limbed dwarfism), abnormal facial features, and/or skeletal malformations.
Characteristic facial features may include an abnormally large head (macrocephaly), unusual prominence of the forehead (frontal bossing), a low nasal bridge, and/or underdevelopment of the middle portion of the face (midface hypoplasia).
Skeletal malformations may include unusually short fingers and toes (brachydactyly), abnormally increased backward curvature of the spine (lordosis), legs that bow outward (genu varum), and/or narrowing (stenosis) of the spine.
Additional abnormalities may include limited extension of the elbows and hips, diminished muscle tone (hypotonia), and/or frequent infections of the middle ear (otitis media).

11. Related Disorders :
Hypophosphatasia is a rare disorder characterized by defective bone hardening (mineralization) resulting in weakened bones.
The long bones of the arms and legs may be abnormally thick, short and bowed.
Affected infants may also have an abnormally small head (microcepahly). Many adults with hypophosphatasia have short stature.
Hypophosphatasia is inherited as an autosomal recessive trait.

12. Related Disorders :
Pyknodysostosis is a rare disorder characterized by increased density of bones (osteosclerosis), short stature, an underdeveloped lower jaw (mandible), and dental abnormalities.
Affected individuals often have fragile bones and may be prone to stress fractures.
Pyknodysostosis is inherited as an autosomal recessive trait.

13. Diagnosis : Clinical evaluation Detailed patient history
Iidentification of characteristic symptoms and a variety of specialized tests.
Surgical removal and microscopic examination (biopsy) of the skin may be done to determine whether abnormalities of collagen are present.
A blood sample may be taken and tested to detect the presence of the genetic mutation that causes OI.

14. Diagnosis : Amniocentesis, and/or chorionic villus sampling (CVS).
Ultrasound studies may reveal characteristic findings such as fractures or bowing of the long bones.
During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied.
During chorionic villus sampling, a tissue sample is removed from a portion of the placenta.
Chromosomal studies performed on this fluid or tissue sample may reveal the genetic mutation that causes OI.

15. Standard Therapies :
Directed toward the specific symptoms that are apparent in each individual.
Treatment is aimed at preventing symptoms, maintaining individual mobility, and strengthening bone and muscle.
Exercise and physical therapy programs have proven beneficial in strengthening muscles, increasing weight-bearing capacity, and reducing the tendency to fracture.
Hydrotherapy proven helpful since moving around in water lessens the chance of fracture.

16. Standard Therapies :
Metal rods are surgically placed in the long bones to prevent fractures (rodding) .
Plastic braces are replacing plaster casts as protective devices permit greater freedom of movement and can be used in water.
Inflatable suits can provide added protection, especially to very young children.

17. Standard Therapies :
Surgery may prove necessary for individuals with severe malformation of the bones of the spine or basilar impression.
Dental procedures may be necessary to correct various dental abnormalities.
Affected individuals, especially adults, should be monitored for hearing impairment often associated with OI.
Genetic counseling may be of benefit for affected individuals and their families.
Other treatment is symptomatic and supportive.

18. Standard Therapies :
Bisphosphonate drugs, growth hormones, and bone marrow transplants.
Fosomax earned an FDA orphan drug designation in 2004.
Growth hormone (GH) therapy has proven beneficial in individuals with mild or moderate forms
(GH has helped improve collagen production and increased growth and bone mineral density).
More research is necessary to determine the long-term safety and effectiveness of bisphosphonate therapy for the treatment of OI.
Marrow mesenchymal cell therapy is currently (2006) being investigated in a clinical study.

19. Further Reference :
osteogenesis imperfecta". Genetics Home Reference. 11 October Retrieved 15 October 2016

20. Q & A
Dr. 熊永萬
Dr. Bear