Clinical Manifestations of Osteogenesis Imperfecta

Osteogenesis imperfecta has the triad of fragile bones, blue sclerae, and early deafness. OI was once divided into “congenita,” the forms detectable at birth, and “tarda,” the forms detectable later in childhood; this did not account for the variability of OI.

The Sillence classification divides OI into four types based on clinical and radiographic criteria. Additional types have been proposed based on histologic distinctions.

Osteogenesis Imperfecta Type I (Mild):
This form is sufficiently mild that it is often found in large pedigrees. Many type I families have blue sclerae, recurrent fractures in childhood, and presenile hearing loss (30–60%). Both types I and IV are divided into A and B subtypes, depending on the absence (A) or presence (B) of dentinogenesis imperfecta. Other possible connective tissue abnormalities include easy bruising, joint laxity, and mild short stature compared with family members. Fractures result from mild to moderate trauma and decrease after puberty.

Osteogenesis Imperfecta Type II (Perinatal Lethal):
These infants may be stillborn or die in the 1st yr of life. Birthweight and length are small for gestational age. There is extreme fragility of the skeleton and other connective tissues. There are multiple intrauterine fractures of long bones, which have a crumpled appearance on radiographs. There are striking micromelia and bowing of extremities; the legs are held abducted at right angles to the body in the “frog-leg position.” Multiple rib fractures create a beaded appearance and the small thorax contributes to respiratory insufficiency. The skull is large for body size with enlarged anterior and posterior fontanelles. Sclerae are dark blue-gray

Osteogenesis Imperfecta Type III (Progressive Deforming):
This is the most severe nonlethal form of OI and results in significant physical disability. Birthweight and length are often low normal. Fractures usually occur in utero. There is relative macrocephaly and triangular facies . Postnatally, fractures occur from inconsequential trauma and heal with deformity. Disorganization of the bone matrix results in a “popcorn” appearance at the metaphyses . The rib cage has flaring at the base, and pectal deformity is frequent. Virtually all type III patients have scoliosis and vertebral compression. Growth falls below the curve by the 1st year; all type III patients have extreme short stature. Scleral hue ranges from white to blue.

Osteogenesis Imperfecta Type IV (Moderately Severe):
Patients with OI type IV may present at birth with in utero fractures or bowing of lower long bones. They may also present with recurrent fractures after ambulation. Most children have moderate bowing even with infrequent fractures. Children with OI type IV require orthopedic and rehabilitation intervention, but they are usually able to attain community ambulation skills. Fracture rates decrease after puberty. Radiographically, they are osteoporotic and have metaphyseal flaring and vertebral compressions. Patients with type IV have moderate short stature. Scleral hue may be blue or white.

Osteogenesis Imperfecta Type V (Hyperplastic Callus), Type VI (Mineralization Defect), and Type VII (Autosomal Recessive):
There has been a proposal to distinguish as distinct types small groups of patients who clinically have OI type IV, but have distinct findings on bone biopsy. They constitute about 5% of OI populations and have negative collagen mutation screening. Type V patients also have hyperplastic callus, calcification of the interosseous membrane of the forearm, and a radiodense metaphyseal band. Type VII maps to chromosome 3p22–24 and is a hypomorphic defect of CRTAP.