Clinical characteristics: Diastrophic dysplasia (DTD) is characterized by limb shortening, normal-sized head, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and contractures of the large joints with deformities and early-onset osteoarthritis. Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. On occasion, the disease can be lethal at birth, but most affected individuals survive the neonatal period and develop physical limitations with normal intelligence.
Diagnosis/testing: The diagnosis of DTD is established in a proband with characteristic clinical and radiographic features and/or biallelic pathogenic variants in SLC26A2 identified by molecular genetic testing. Biochemical studies of fibroblasts and/or chondrocytes may be used in the rare instances in which molecular genetic testing fails to identify SLC26A2 pathogenic variants.
Management: Treatment of manifestations: Cervical spine surgery in infancy restricted to individuals with clinical or neurophysiologic evidence of spinal cord impingement; physical therapy may prevent early joint contractures; in children, physiotherapy and casting to maintain joint positioning and mobility as much as possible; surgical correction of clubfoot when ambulation becomes impossible; undertake orthopedic surgery with caution as deformities tend to recur; postpubertal surgical correction of scoliosis is recommended unless severe spinal deformity is causing respiratory compromise or neurologic signs; total arthroplasty of hips and knees in relatively young adults to decrease pain and increase mobility; treatment of cystic ear swelling is conservative.
Surveillance: Annual monitoring of spinal curvature and joint contractures.
Agents/circumstances to avoid: Obesity, which places an excessive load on the large, weight-bearing joints.
Genetic counseling: DTD is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SLC26A2 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SLC26A2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.
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