David Sillence formulated the classification currently in common use for osteogenesis imperfecta in 1979. [2] Since type I collagen defects were not known to cause OI at that time, the Sillence Classification is an artificial grouping based on clinical and radiographic features. The clinical spectrum of OI ranges from perinatal lethal to a mild form that can present in middle aged adults as premature osteoporosis. All types of OI have autosomal dominant inheritance. [3] Some severe cases were thought to be autosomal recessive at the time the Sillence Classification was formulated, but are now known to be autosomal dominant with parental mosaicism (See Parental Mosaicism, below). Autosomal recessive cases with type I collagen defects are possible, although quite rare. There have been three documented cases, one of which is quite similar to the oim murine model for OI.

Type II OI is the perinatal lethal form. Infants may be stillborn; if they survive birth, they usually die in the first two months of life. [4] Some infants with type II OI may live for as long as a year, but eventually do succumb to multiple pneumonias or respiratory insufficiency. The limbs, especially the legs, are short with severe bowing deformities. Most often the legs are abducted into the classic “frog leg position”. The cranium is relatively large for the trunk and is very poorly ossified. The anterior fontanelle is large, and often extends frontally to the forehead and laterally along the sagittal suture. The posterior fontanelle is often open as well. The presence of two enlarged fontanelles frequently results in ossification only along the lateral plates and for a fingertip breadth at the crown. The infants tend to have flat triangular facies with a small beaked nose and dark blue-gray sclerae. The thorax is usually deformed with a narrow apex. Radiographic examination reveals multiple in utero fractures in various stages of healing. There may be beads of callus on the ribs, which are quite gracile. The long bones are very osteoporotic with minimal to no cortex. Upper extremity long bone morphology is better than that of the lower extremities. The lower long bones are crumpled as well as fractured and are abnormally modeled, with a cylindrical shape. Thus, the defect in type I collagen affects the development as well as the mineralization of the skeleton.

Type III OI, also known as the Progressive Deforming type [1], is the most severe form of OI compatible with survival beyond infancy and is severely handicapping. Individuals with type III OI can have a full life span, however, a significant proportion succumb to respiratory or neurological complications, either during childhood or in early to middle adult years. The long bones of individuals with type III OI are soft as well as fragile and can have bowing deformities of 70-90°, caused either by the tension of normal muscle on the bone, or from angulated healing of fractures. Long bones have a cylindrical shape with more modeling of the metaphysis than in type II; by late childhood there is often exaggerated metaphyseal flaring accompanied by a slender diaphysis. [5] Fractures can occur from activities of daily living; there may be hundreds of fractures in a lifetime. DEXA z-scores are in the range of –5 to –7 SD. Body proportions are better preserved than in type II OI, with less shortening of the extremities relative to the trunk. The calvarium is almost always relatively macrocephalic for the body and frequently measures greater than 95% for age, though occasionally children will have a normal or smaller than average HC for age. The midface is flat with frontal bossing. Children with type III OI almost always develop chest wall abnormalities; pectus carinatum is more frequent and less detrimental to pulmonary status than pectus excavatum. Virtually all children with OI type III will also develop significant scolisis. Without aggressive intervention, these individuals will be wheelchair bound.

Type IV OI is the moderately severe type. The skeletons of these individuals are brittle, not soft. On average, people with type IV OI have dozens of fractures. Most fractures occur either prior to puberty or beyond middle age, with the intervening years relatively protected by sex steroids. Individuals are significantly osteoporotic, with DEXA z-scores in the range of –3 to –5 SD. With medical intervention these individuals can expect to be community ambulators and have an essentially normal life span. Body proportions approach normal, although the legs are still short for the trunk and the cranium is relatively macrocephalic. Individuals are divided into types A and B by the Sillence classification, based on the presence or absence of dentinogenesis imperfecta. [6] Vertebral compressions in childhood and laxity of paraspinal muscles may lead to significant scoliosis.

In conjunction with discussion of type IV OI, it is appropriate to consider the recent publications on types V and VI OI. Although these types continue the numerical system of the Sillence classification, they have a different basis. These individuals fall within the phenotypic range of type IV OI, as defined by the Sillence classification, but are primarily distinguished from patients with type IV OI by iliac crest histomorphometry. In type V, the distinctive histology is irregular arrangement or a meshlike appearance of the lamellae. Patients also have hypertrophic callus, dense metaphyseal bands and ossification of the interosseus membranes of the forearm. Though individuals initially were distinguished on histologic grounds, the presence of unique phenotypic features suggests that this may be a distinct subgroup within the current OI classification. The type I collagen protein of these patients has normal electrophoretic mobility, and no mutations have been detected at the gene level. [7] Therefore, the cause of type V OI may be defects in a molecule other than type I collagen. The proposed type VI OI is distinguished solely on histology criteria. [8] Since it has no distinctive phenotype within the OI spectrum, it may be premature to split these patients off from type IV OI.

Patients with type I OI have a distinctly milder form of the disease, which is generally not detectable at birth. Patients with type I OI tend to present with early osteoporosis; DEXA z-scores range from –1 to –3. Patients may have their first fracture in the pre-school years, for example when attaining ambulation. They may also have a series of fractures in the pre-pubertal years due to mild trauma. Fractures generally decrease dramatically in the post-pubertal years. Patients with type I OI have normally modeled bone and may have mild bowing of long bones and minimal central vertebral compressions. They are often a few inches shorter than same gender relatives. Leg length may be disproportionately short. Like type IV, type I is divided into A and B subtypes based on the presence or absence of dentinogenesis imperfecta. [6] Blue scleral hue is a defining feature in the Sillence classification, though in actuality it may be present or absent. These patients are expected to be spontaneous ambulators, but may have some mild delay of gross motor skills. They can be expected to have a full life span, limited only by greater vulnerability to accidental trauma.