Diastrophic Dysplasia

Autosomal recessive inherited form of short-limb dwarfism associated with spine anomalies.

Diastrophic Dwarfism; Diastrophic Nanism Syndrome.

1:100,000 live births, with an approximately three times higher incidence in Finland.

Transmission is autosomal recessive, with a broad phenotypical range. The responsible gene maps to 5q32-q33.1 (also called SLC26A2).

The defect on chromosome 5 affects the diastrophic dysplasia sulfate transporter (DTDST) and leads to depletion of intracellular sulfate and insufficient sulfation of sulfated macromolecules such as cartilage matrix proteoglycans, which results in abnormally soft cartilage with decreased resistance to stress.

Made by the clinical findings and molecular genetic testing.

This form of rhizomelic (short-limb) dwarfism is characterized by a proportionate shortening of the tubular bones, which are approximately 50% of the normal length. Abduction of the thumbs results from a short and oval-shaped first metacarpal bone, which gives it the aspect of a “hitchhiker thumb.” Severe clubfoot deformity with luxation of the big toes and ulnar deviation of the hands are typical. These findings, which are present in prenatal ultrasonographs, make very likely the diagnosis of diastrophic dysplasia. A patient may suffer from hyperlaxity with recurrent dislocations of some joints, while other joints show stiffness and contractures. During the first 2 to 5 weeks of life, more than 80% of patients suffer from swelling and inflammation of the ear cups with subsequent calcification and “cauliflower”-like ears. The palate is high arched and broad, and cleft palate (complete, partial or submucous, double or bifid uvula) may occur in up to 25% of patients. The abnormally soft cartilage is responsible for laryngotracheobronchomalacia and often causes respiratory distress. Spinal deformities, such as mid-cervical kyphosis with potential compression of the medulla, cervical spina bifida occulta, and scoliosis (with lung volumes inversely correlated to the angle of scoliosis) with decreased chest mobility, contribute to the respiratory problems. In fact, respiratory failure is responsible for the increased mortality in the first months of life. Although cervical kyphosis resolves spontaneously in more than 90% of patients, progression to quadriplegia and death has been reported. The median adult height in a Finnish study of 121 affected men and women was 135 cm (53.1 in) and 129 cm (50.8 in), respectively. Most of the patients are mentally normal, but as a consequence of the orthopedic problems, motor skills are delayed and their exercise tolerance is reduced secondary to respiratory problems.

The pulmonary situation should be optimized as much as possible before surgery, and the need for postoperative mechanical ventilation should be anticipated. A chest radiograph should be obtained. Cervical spine anomalies are frequent and require a thorough clinical and radiologic evaluation. Lateral flexion and extension radiograph and/or MRI of the neck may be necessary to evaluate the grade of spinal compression.

Death as a result of anesthetic complications has been described. If tracheal intubation is required, either inline cervical stabilization or fiberoptic intubation is recommended. Careful handling and positioning of these patients are mandatory in the presence of cervical instability, contractures, and skeletal deformities. Depending on the type of surgery, somatosensory evoked potential during induction, but especially for positioning, has been recommended in patients with cervical instability to monitor for signs of cord compression. If tracheal intubation is not mandatory, a face mask or alternatively a laryngeal mask may be a good alternative, avoiding not only tracheal but also cervical spine manipulations. However, continuous positive airway pressure may be required secondary to laryngotracheobronchomalacia. Abnormalities of tracheal, laryngeal, and bronchial cartilage resulting in airway collapse and death have been described.

Cervical instability may result in spinal cord compression and consecutive weakness of distal muscles. Consequently, succinylcholine could lead to a hyperkalemic response.

Desbuquois Syndrome: Autosomal recessive osteochondrodysplastic disease with typical skeletal anomalies and high mortality in the first year of life.

Larsen Syndrome: Congenital dysmorphic syndrome associated with characteristic anomalies of face, hands, and feet, and multiple congenital dislocations. Spine, airway, and cardiac abnormalities are associated.

Chondrodysplasia Giant Cell type: Lethal form of chondrodysplasia characterized by rhizomelic limb shortening with giant cell chondrodysplasia.

Thanatophoric Dwarfism: Severe form of micromelic dwarfism with narrow thorax. Death generally occurs in the first hours of life.