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At a glance

Severe chondrodysplasia caused by the defective formation of type II collagen characterized by dwarfism, skeletal anomalies, and often cleft palate and severe myopia/blindness. It is characterized by the dumb-bell shape of shortened long tubular bones. The short stature, enlarged knees, and cleft palate are usually present at birth. Other features may appear only after 2 or 3 years of age.

Synonyms

Kniest Syndrome; Metatropic Dysplasia Type II (name given by “accident,” because Metatropic Dwarfism is a completely different entity); Swiss Cheese Cartilage Syndrome; Pseudometatropic Dysplasia.

History

This medical condition was first diagnosed by Dr Wilhelm Kniest, a German pediatrician, in 1952. Dr Kniest noticed an association between severe restricted joint mobility, short stature, and blindness in a 50-year-old patient.

Incidence

This condition is very rare and has been suggested to occur in less than 1 in 1,000,000 people worldwide. Males and females equally affected.

Genetic inheritance

Autosomal dominant inheritance. The genetic defect has been mapped to 12q13.11-q13.2. This rare form of dwarfism is caused by a mutation in the COL2A1 gene on chromosome 12. This gene is responsible for producing type II collagen. However, it is believed that many cases are sporadic.

Pathophysiology

Mutations of this genetic segment lead to abnormal type II collagen with specifically shorter monomers. Grossly, the cartilage feels soft. Histologically, the cartilage has lacunae throughout, giving it the appearance of “Swiss Cheese.” As a result, all tissues containing cartilage are affected with respect to growth, structure, and function.

Diagnosis

Characteristic phenotype. Some patients excrete keratan sulfate (a mucopolysaccharide) in the urine. Cartilage histology and electron microscopy are characteristics.

Clinical aspects

Phenotype is apparent at birth. Craniofacial abnormalities include macrocephaly, flat midface, flat nose root, and cleft palate. Occasional association with Pierre-Robin Syndrome has been reported. Tracheal cartilage is abnormal, and tracheomalacia may occur as a result. The chest may be short and narrow, but ventilation and perfusion of the lungs usually remain unaffected. The vertebral column often has platyspondylia with anterior wedging of the vertebral bodies, coronal clefting of the thoracolumbar vertebral bodies, and occipitoatlantal instability. Kyphoscoliosis and/or lumbar hyperlordosis may develop. In an extensively studied patient, there was bony fusion between the anterior arch of the atlas and the odontoid and between the posterior arch of the atlas and the cranial base. Growth usually is retarded. The limbs are characteristically very short secondary to short tubular bones. The epiphyses are large and deformed and the metaphyses broad resulting in so-called “dumb-bell” shape, as a consequence of delayed epiphyseal ossification resulting in mega-epiphyses. The joint space is narrow with limited joint mobility. Early-onset myopia, retinal detachment, and sensorineural hearing ...

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