�ֲ���ý

Metatropic dysplasia is caused by a mutation in the Transient Receptor Potential Cation Channel Subfamily V Member 4 (TRPV4) gene. The TRPV4 gene encodes a transmembrane calcium channel which plays an important role in cartilage, bone and neuromuscular function. In metatropic dysplasia, the TRPV4 channel is overactive.

Metatropic dysplasia has autosomal dominant inheritance. 

Initially, individuals have shortened limbs with a relatively average-sized trunk (short-limbed dwarfism). As the child gets older and the condition progresses, kyphoscoliosis of the spine develops that decreases trunk height (short-trunk dwarfism). Apparent shortening of the limbs also occurs over time, due to progressive joint contractures.

Face and Skull

• Elongated faces
• Prominent forehead
• Relative macrocephaly
• Average intelligence

Trunk, Chest and Spine

• Small and narrow chest
• Pectus carinatum (chest bone sticking out more than average) or pectus excavatum (depressed breast bone)
• Progressive kyphoscoliosis
• In infancy, some children can have a cartilaginous prolongation of the tailbone

Arms and Legs

• Rhizomelic shortening
• Significantly shortened limbs
• Enlarged joints
• Progressive joint contractures during childhood

X-Ray Characteristics

The radiographic features of metatropic dysplasia include small, flat, diamond-shaped vertebral bodies in early infancy. Later, platyspondyly and anterior wedging of vertebral bodies are characteristic.

The pedicles are overfaced. The lateral border of the vertebral body appears outside the lateral edge of the pedicle.

The thorax is narrow and ribs are short, in both infancy and early childhood.

The long bones are shortened with metaphyseal flare and epiphyseal dysplasia, leading to a “dumbbell” appearance.

Metatropic dysplasia is diagnosed by its clinical and radiographic characteristic features. Genetic testing of the TRPV4 gene can be performed to confirm the diagnosis.

Neck

Atlantoaxial instability and cervical stenosis are very common in metatropic dysplasia. Flexion and extension X-rays of the neck should be performed at diagnosis and at periodic intervals thereafter. Further information can be obtained by means of an MRI scan, typically done with flexion and extension views as well. If cervical instability is progressive or symptomatic, surgical fusion with decompression may be necessary.

Spine

Kyphoscoliosis is commonly seen in early childhood. It is often severe and rapidly progressive. The spine should be imaged early and followed-up at regular intervals. Bracing may be of some benefit in younger children with smaller curves.

The timing of spinal decompression and fusion for scoliosis in metatropic dysplasia is dependent upon the severity of the curve, curve progression, age and risk of injury to the spinal cord. The status of the respiratory system may also dictate the timing of surgery, especially in the younger, more severely affected children

Limb Deformities

The limbs are short with significant joint contractures. Treatment is dictated by walking ability, amount of functional compromise and symptoms. Common problems include hip and knee flexion contractures and genu valgum. Some individuals can have ligamentous laxity.

Fractures

In one study from our center, we found that 40% of our patients with metatropic dysplasia had a fracture, with 25% having two or more.

Respiratory

Respiratory difficulties result from a stiff, small and narrow rib cage as well as tracheal and bronchomalacia in some children. Prolonged breathing difficulties may warrant a tracheostomy and long-term ventilatory support. Other serious causes of respiratory issues are spinal cord compression and neuromuscular disease. Lung function tests and sleep studies are frequently used to diagnose breathing problems in skeletal dysplasias. Regular review by a pulmonologist is recommended.

Hearing Loss

Sensorineural hearing loss can occur in metatropic dysplasia, and routine hearing assessments are necessary.

For individuals with metatropic, any change in walking ability, endurance or breathing should have further assessment by a medical provider to rule out spinal cord compression. Specific neurological symptoms such as tingling or numbness in the arms or legs, weakness, shooting leg or arm pain, or problems controlling bladder/bowel function should be investigated further.

One should also watch out for progressive curvature of the spine.

When undergoing any surgical procedure, management of the airway by an anesthesiologist is very important, as difficult airway is common, especially if their cervical spine has been fused.

1. Krakow D, Vriens J, Camacho N, Luong P, Deixler H, Funari TL, Bacino CA, Irons MB, Holm IA, Sadler L, Okenfuss EB, Janssens A, Voets T, Rimoin DL, Lachman RS, Nilius B, Cohn DH. Am J Hum Genet. 2009 Mar;84(3):307-15.
2. Spranger JW, Brill, PW, Hall C, Nishimura G, Superti-Furga, A, Unger, S. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2018.
3. McCray BA, Schindler A, Hoover-Fong JE, et al. Autosomal Dominant TRPV4 Disorders. 2014 May 15 [Updated 2020 Sep 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
4. Leet AI, Sampath JS, Scott CI Jr, MacKenzie WG. Cervical spinal stenosis in metatropic dysplasia. J Pediatr Orthop. 2006 May-Jun;26(3):347-52.
5. Bober MB, Duker AL, Carney M, Ditro CP, Rogers K, Mackenzie WG. Metatropic dysplasia is associated with increased fracture risk. Am J Med Genet A. 2016 May;170A(5):1373-6
6. Theroux MC, Lopez M, Olszewsky PJ, DiCindio S, Arai L, Ditro C, Bober MB, Olla OO, Uejima T, West DW, Mackenzie WG. Metatropic dysplasia-a skeletal dysplasia with challenging airway and other anesthetic concerns. Paediatr Anaesth. 2017 Jun;27(6):596-603.