Kniest Syndrome

Severe chondrodysplasia caused by the defective formation of type II collagen characterized by dwarfism, skeletal anomalies, and often cleft palate and deafness.

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

Unknown, but very rare. Males and females equally affected.

Autosomal dominant inheritance. The genetic defect has been mapped to 12q13.11-q13.2. Many cases, however, seem to be sporadic.

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.

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

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 “dumbbell” 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 loss are common findings. Patients often present for repair of umbilical and inguinal hernias.

Assessment for potential difficult intubation. Presence of respiratory distress, especially stridor, may signify tracheomalacia. Preoperative arrangement for close postoperative supervision and the possibility for postoperative mechanical ventilation is advisable if one or both of the above conditions are present. Documentation of cervical spine instability with lateral flexion and extension cervical spine radiographs, if possible.

Potentially difficult airway management. Passage of nasotracheal tubes may be difficult if midface hypoplasia is present. If there is atlantooccipital instability, utmost care must be taken to avoid excessive, if any, movement of the cervical spine in an anesthetized patient. Manual inline stabilization of the cervical spine during direct laryngoscopy and tracheal intubation attempts is crucial. Techniques that minimize movement, such as fiberoptic intubation, are the best approach. Awake intubation in a cooperative patient, with documentation of intact neurologic status after intubation and positioning, is ideal. The combination of difficult airway with an unstable cervical spine is potentially disastrous, so anesthetic techniques that require manipulation of the airway should be avoided if possible. However, central neuraxial anesthesia techniques could be difficult given the anatomical anomalies of the spine. Airway obstruction can occur intraand postoperatively because of tracheomalacia. Judicious use of opioids and other sedating drugs and close supervision with oxygen saturation and apnea monitoring in the postoperative period are highly recommended. Careful positioning of stiff and painful joints is important for preventing pressure sores and nerve palsies. Patients with visual or hearing impairment may suffer from a greater degree of anxiety and may not be as cooperative.

Use of agents that may affect respiration and airway patency should be used cautiously in patients with abnormal airway anatomy. Avoid neuromuscular blockers and maintain spontaneous ventilation until the airway has been secured.

Achondrogenesis: Short trunk and limbs, large head, and usually a cleft palate and small chin; also a result of defective type II collagen.

Metatropic Dysplasia type I: Severe dwarfism with short arms and legs, narrow thorax, short ribs, kyphoscoliosis, joint anomalies, and tail-like skin fold over sacrum; both autosomal dominant and autosomal recessive forms exist.

Morquio Disease: Autosomal recessive mucopolysaccharidosis with dwarfism, kyphosis, platyspondyly, and severe disability but normal intelligence.