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Diastrophic dysplasia is caused by mutations in the gene coding for a sulfate transporter protein. Sulfate transport is essential for typical cartilage function. This protein is called diastrophic dysplasia sulfate transporter (DTDST) and was first identified by Hastbacka and colleagues in 1994.¹ The DTDST or SLC26A2 gene is located on chromosome 5 (5q31-q34). Changes in the DTDST gene cause a reduction in sulfate transported into the cells and subsequent undersulfation of cartilage. The abnormal cartilage structure is responsible for the medical issues associated with diastrophic dysplasia.³

Diastrophic dysplasia is inherited as an autosomal recessive condition.³

Diastrophic dysplasia is a short-limbed form of disproportionate short stature. A person with diastrophic dysplasia may have some or many physical characteristics associated with the condition. Intelligence is typically average.³

Face and Skull

• High, broad forehead
• Long and broad philtrum
• Cleft palate (approximately 33% of children)
• Capillary hemangioma called an "Angel's kiss" in the midforehead region
• Cystic swellings of the outer ear(s) often occur in the first weeks of life, resulting in the characteristic “cauliflower ear”

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Trunk, Chest and Spine

• Cervical kyphosis in infancy
• Typically scoliosis is not present in infancy, but with age becomes present

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Arms and Legs

• Mesomelic shortening of limbs
• "Hitchhiker’s thumb" due to changes in the joint that causes the thumb to deviate outward
• Limited movement of the fingers due to symphalangism
• Joint dislocations and joint contractures����
• Significant foot and ankle deformity, which while often termed clubfoot, is distinct from classic clubfoot��

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X-Ray Characteristics

• Shortening and metaphyses widening of the long bones
• Epiphyseal dysplasia with flattening and delaying ossification
• Crescent-shaped and flattened epiphyses of the proximal tibias are triangular and larger than those of the of the distal femoral epiphyses
• Cervical kyphosis is often present at birth and can spontaneously resolve
• Thoracolumbar kyphoscoliosis is observed at different ages and may be progressive
• Moderate narrowing of the interpediculate distances within the lower lumbar segments of the spine

Diastrophic dysplasia is typically recognized at birth based on physical characteristics and radiographic evaluation. Children with a milder presentation may not be diagnosed until a later age. Genetic testing can also be recommended if a skeletal dysplasia such as diastrophic dysplasia is suspected during a prenatal ultrasound. Genetic testing can be performed on fetal DNA from an amniocentesis sample.

In parents who already have children with diastrophic dysplasia, an ultrasound scan or genetic testing (using DNA from amniocentesis or chorionic villus sampling) offers the possibility of prenatal diagnosis of this condition.

Cervical Kyphosis

Cervical kyphosis is present in 30–50% of individuals. It is due to hypoplasia of the vertebral bodies and progressive degenerative changes in the intervertebral joints. Cervical kyphosis can range from mild to severe. In children with mild cervical kyphosis, these concerns often resolve without treatment. A predisposition to spinal cord compression is seen in severe cases, and surgery may be necessary to alleviate it. If this is performed, a halo and vest device are typically used after surgery to support the neck until healing or fusion is achieved. It is important that all children with diastrophic dysplasia are monitored for cervical kyphosis.

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Thoracolumbar Scoliosis

Scoliosis is very common in diastrophic dysplasia. There appears to be several developmental patterns of scoliosis. One pattern is that of a kyphoscoliosis�� which develops in infancy and is rapidly progressive. A second pattern is that of a kyphoscoliosis which develops at an older age, tends to progress more slowly, and can accelerate during puberty. The third pattern is that of a kyphoscoliosis which is also later in onset, but is mild and non-progressive. Non-invasive treatments can involve bracing and serial casting. Surgical management can include growing rod systems and ultimately spinal fusion procedures.

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Foot Deformities

Foot deformity in diastrophic dysplasia is quite common and is often termed “clubfoot.” The deformity, however, is quite distinct and more complex than a classic clubfoot deformity. There are differences in both the hindfoot (towards the ankle) and the forefoot (towards the toes). The hindfoot tends to have decreased range of motion and is locked into a dorsiflexed position. The forefoot is angulated towards the midline. Taken together the foot has a “serpentine” appearance.

Types of treatment for diastrophic feet are individualized and based on an individual’s unique anatomy. It is important for the foot to be regularly monitored by an experienced pediatric orthopedic surgeon so appropriate treatments can be started at the right time. Serial casting is often utilized in infancy. Surgical correction is often required to achieve a foot position where the foot and heel can simultaneously be on the floor during walking. Recurrence is common and additional surgeries may be required. Special orthotic shoes are often beneficial.⁸

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Changes to the Lower Extremities

Joint contractures, progressive subluxation of the hips and dislocation of the knees occur due to changes in the joints. If those changes interfere with walking, surgery may be recommended at the hips and/or knees to improve function. Hip or knee replacement surgery is usually necessary in early to mid-adulthood and typically has successful results. Due to underlying changes in the cartilage of patients with diastrophic dysplasia, degenerative joint disease (arthritis) is also common.⁹��

Tracheobronchomalacia��

The walls of the trachea and bronchi are stiffened by cartilage. Due to the abnormalities which exist in cartilaginous structures in individuals with diastrophic dysplasia, the airway may be affected. The walls of the airway may be weakened and could collapse under certain circumstances. These issues are going to be more commonly seen in infancy. In extreme situations, tracheostomy and ventilatory support may be necessary.��

Diastrophic dysplasia requires a multidisciplinary team approach. Regular assessment by a coordinated team which includes an orthopedist, complex-care pediatrician, pulmonologist, neurosurgeon, and physical therapist will provide the most comprehensive treatment. Specialists should be monitoring for:

• Skeletal deformities in the cervical, thoracic and lumbar spine and lower extremities
• Growth, development and weight gain
• Tracheobronchomalasia
• Cleft palate care as needed

1. Hastbacka, J.; Sistonen, P.; Kaitila, I.; Weiffenbach, B.; Kidd, K. K.; de la Chapelle, A.: A linkage map spanning the locus for diastrophic dysplasia (DTD). Genomics 11: 968-973, 1991.
   
2. Poussa, Mikko. Merikanto, Juhani. Ryoppy, Soini. Marttinen, Eino. Kaitila, Ilkka. The Spine in Diastrophic Dysplasia. Spine; 16(8):881-887. 1991.��
3. Bonafé L, Mittaz-Crettol L, Ballhausen D, et al. Diastrophic Dysplasia. 2004 Nov 15 [Updated 2013 Jul 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.��
4. 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.
5. Remes VM, Marttinen EJ, Poussa MS, Helenius IJ, Peltonen JI Cervical spine in patients with diastrophic dysplasia--radiographic findings in 122 patients. Pediatr Radiol. 2002 Sep;32(9):621-8.��
6. Jalanko T, Remes V, Peltonen J, Poussa M, Helenius I. Treatment of Spinal Deformities in Patients With Diastrophic Dysplasia. Spine (Phila Pa 1976). 2009;34(20):2151-2157
7. Al Kaissi A, Kenis V, Melchenko E, et al. Corrections of Lower Limb Deformities in Patients with Diastrophic Dysplasia. Orthop Surg. 2014;6(4):274-279
8. Bayhan IA, Er MS, Nishnianidze T, Ditro C, Rogers KJ, Miller F, Mackenzie WG. Gait Pattern and Lower Extremity Alignment in Children With Diastrophic Dysplasia. J Pediatr Orthop. 2016 Oct-Nov;36(7):709-14.��
9. Weiner, DS, Jonah, D and Kopits, S.�� The 3-Dimensional Configuration of the Typical Foot and Ankle in Diastrophic Dysplasia. J Pediatr Orthop. 2008. 28(1):60-7.