What kinds of O.I. are there?

Clinical Features
The characteristic features of O.I. vary greatly from person to person, even among people with the same type of O.I., and even within the same family. Not all characteristics are evident in each case. The majority of cases of O.I. (possibly 85-90 %) are caused by a dominant mutation in a gene coding for type I collagen (Types I, II, III, and IV in the following list). Types VII and VIII are newly identified forms that are inherited in a recessive manner. The genes causing these two types have been identified. Types V and VI do not have a type 1 collagen mutation, but the genes causing them have not yet been identified. The general features of each known type of O.I. are as follows:

Type I

• Most common and mildest type of O.I.
• Bones fracture easily. Most fractures occur before puberty.
• Normal or near-normal stature.
• Loose joints and muscle weakness.
• Sclera (whites of the eyes) usually have a blue, purple, or gray tint.
•  Triangular face.
• Tendency toward spinal curvature.
• Bone deformity absent or minimal.
• Brittle teeth possible.
• Hearing loss possible, often beginning in early 20s or 30s.
• Collagen structure is normal, but the amount is less than normal.

Type II

• Most severe form.
• Frequently lethal at or shortly after birth, often due to respiratory problems. 
• Numerous fractures and severe bone deformity.
• Small stature with underdeveloped lungs.
• Tinted sclera.
• Collagen improperly formed.

Type III

• Bones fracture easily. Fractures often present at birth, and x-rays may reveal healed fractures that occurred before birth.
• Short stature.
• Sclera have a blue, purple, or gray tint.
• Loose joints and poor muscle development in arms and legs.
• Barrel-shaped rib cage.
• Triangular face. 
• Spinal curvature.
• Respiratory problems possible.
• Bone deformity, often severe.
• Brittle teeth possible.
• Hearing loss possible.
• Collagen improperly formed.

Type IV

• Between Type I and Type III in severity.
• Bones fracture easily. Most fractures occur before puberty.
• Shorter than average stature.
• Sclera are white or near-white (i.e. normal in color).
• Mild to moderate bone deformity.
• Tendency toward spinal curvature.
• Barrel-shaped rib cage.
• Triangular face.
• Brittle teeth possible.
• Hearing loss possible.
• Collagen improperly formed.

By studying the appearance of O.I. bone under the microscope, investigators noticed that some people who are clinically within the Type IV group had a distinct pattern to their bone. When they reviewed the full medical history of these people, they found that groups had other features in common. They named these groups Types V and VI O.I. The mutations causing these forms of O.I. have not been identified, but people in these two groups do not have mutations in the type I collagen genes.

Type V

• Clinically similar to Type IV in appearance and symptoms of O.I.
• A dense band seen on x-rays adjacent to the growth plate of the long bones.
• Unusually large calluses (hypertrophic calluses) at the sites of fractures or surgical procedures. (A callus is an area of new bone that is laid down at the fracture site as part of the healing process.)
• Calcification of the membrane between the radius and ulna (the bones of the forearm). This leads to restriction of forearm rotation. 
• White sclera.
• Normal teeth. 
• Bone has a “mesh-like” appearance when viewed under the microscope. 
• Dominant inheritance pattern

Type VI

• Clinically similar to Type IV in appearance and symptoms of O.I.
• The alkaline phosphatase (an enzyme linked to bone formation) activity level is slightly elevated in O.I. Type VI. This can be determined by a blood test. 
• Bone has a distinctive “fish-scale” appearance when viewed under the microscope.
• Diagnosed by bone biopsy.
• Whether this form is inherited in a dominant or recessive manner is unknown, but researchers believe the mode of inheritance is most likely recessive.
• Eight people with this type of O.I. have been identified.

Recessive Forms of OI
After years of research, two forms of O.I. that are inherited in a recessive manner were discovered in 2006. Both types are caused by genes that affect collagen formation. These forms provide information for people who have severe or moderately severe O.I. but who do not have a primary collagen mutation.

Type VII

• The first described cases resemble Type IV O.I. in many aspects of appearance and symptoms.
• In other instances the appearance and symptoms are similar to Type II lethal O.I., except infants had white sclera, a small head and a round face.
• Short stature.
• Short humerus (arm bone) and short femur (upper leg bone) 
• Coxa vera is common (the acutely angled femur head affects the hip socket).
• Results from recessive inheritance of a mutation to the CRTAP (cartilage-associated protein) gene. Partial function of CRTAP leads to moderate symptoms while total absence of CRTAP was lethal in all 4 identified cases.

Type VIII

• Resembles lethal Type II or Type III O.I. in appearance and symptoms except that infants have white sclera.
• Severe growth deficiency.
• Extreme skeletal under mineralization.

Caused by a deficiency of P3H1 (Prolyl 3-hydroxylase 1) due to a mutation to the LEPRE1 gene.