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Kniest dysplasia is a severe type II collagenopathy characterized by a short trunk and limbs, prominent joints and midface hypoplasia (round face with a flat nasal root). Prevalence is unknown. The disease is apparent from birth. Cleft palate (sometimes associated with Pierre-Robin syndrome, see this term), kyphoscoliosis, premature osteoarthritis, severe myopia and deafness are common findings. Stature varies but is often severely affected. Intelligence is usually normal. The disease is transmitted as an autosomal dominant trait and is caused by mutations in the COL2A1 gene (12q13.11-q13.2) encoding type II collagen. Diagnosis is made on the basis of radiologic features including large and deformed epiphyses, absence of the femoral head, enlargement of the superior metaphysis of the femur, platyspondyly and other vertebral malformations. Pathological studies of the cartilage reveal the presence of intracytoplasmic inclusions in chondrocytes and a highly vacuolated matrix. Forms of spondyloepiphyseal dysplasia and metatropic dysplasia (see these terms) constitute the principle differential diagnoses. In young patients, clinical and radiological features overlap with those of OSMED (see this term), but in the latter myopia is absent. Most cases are due to de novo heterozygous COL1A2 mutations but affected parents should be informed of a recurrence risk of 50%. Molecular prenatal diagnosis is possible for families in which the disease-causing mutation has already been identified. Micromelia may be detected during the second trimester of the pregnancy and fetal CT scan may be a useful tool for diagnosis. Management is supportive only. Prognosis depends on the extent of the joint malformations and vertebral anomalies. |