NeurometPlus

Incidence

Autosomal dominant. Caused by mutations in the collagen I, alpha-1 gene and alpha-2 gene.

Clinical Characteristics

Perinatal lethal osteogenesis imperfecta is designated as type II. Its main characteristics are severe dwarfism, thick bones, deformed craniofacies, small chest and infantile death. Type II osteogenesis imperfecta often produces thickened limb bones that can be recognized by skeletal radiography; early recognition is important because the very short, deformed limbs portend a limited life span and developmental potential. Survival of patients with type II osteogenesis imperfecta is often determined by the degree to which rib fractures cause lung problems. The poor outlook for these children is magnified by the recent demonstration of brain abnormalities due to abnormal collagen in blood vessels and abnormal brain circulation. The complications of osteogenesis imperfecta vary greatly by type. Patients with type II disease are often recognized prenatally, and exhibit extremely short stature with multiple prenatal fractures. Their sclerae (whites of the eyes) will be dark gray or blue, and the skeletal and central nervous system complications are extremely severe. Perinatal lethal. Premature birth. Nonimmune hydrops. Survival greater than one year rare. Gonadal and somatic mosaicism reported in parent. Ultrasound detection in second trimester of pregnancy Type II was considered autosomal recessive. Now it is realized that all major types of osteogenesis imperfecta involve mutations in the genes for type I collagen, with type II osteogenesis imperfecta caused by new mutations in critical regions of the collagen molecule. Occasional type II families in which normal parents have several affected children are thought to represent germinal mosaicism. Normal parents of children with the severe type II osteogenesis imperfecta have a surprisingly high recurrence risk of 6% due to sperm or eggs that carry the mutation.

Precipitants

none

Provocation Tests

none

Diagnostic Procedures

Skeletal x-rays are often diagnostic, but biochemical and DNA testing for collagen abnormalities provide the most definitive diagnosis when they reveal an abnormality. Although DNA testing can be performed from blood samples, the variety of mutations in the osteogenesis imperfectas is too great to allow comprehensive screening. A better method for testing is to analyze collagen synthesis in cultured fibroblasts from skin biopsy. If an abnormality of collagen synthesis is detected in skin fibroblasts, then DNA testing for collagen gene abnormalities can be tried.