Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate
dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature
osteoarthritis, and craniofacial manifestations. The
craniofacial abnormalities include
tracheomalacia, midface hypoplasia,
cleft palate, early onset
myopia,
retinal detachment, prominent eyes, and
sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in
type II collagen splicing sequences. Mutations have been identified in the COL2A1 (
type II collagen) gene between exons 12 and 24.
Type II collagen is the predominant structural
protein in cartilage, and mutations in this
collagen account for the
Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had
tracheomalacia with
airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were
diastase-resistant and were also highlighted on
Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical
glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated
type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal
type II collagen in the matrix and the severity of the phenotype. With low levels of normal
type II collagen, the phenotypic manifestations become more severe, such as in
achondrogenesis type II. Both the quantity and quality of
type II collagen modulates the phenotypic expression of type II collagenopathies.