Diastrophic Dysplasia

CLINICAL CHARACTERISTICS: Diastrophic dysplasia (DTD) is characterized by limb shortening, normal-sized skull, 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 rests on a combination of clinical, radiologic, and histopathologic features. The diagnosis is confirmed by molecular genetic testing of SLC26A2, the only gene in which pathogenic variants are known to cause DTD. 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: In children, physiotherapy and casting to maintain joint positioning and mobility as much as possible; surgical correction of clubfoot when ambulation becomes impossible; cervical spine surgery restricted to individuals with clinical or neurophysiologic evidence of spinal cord impingement; surgical correction of scoliosis in those at risk for rapid increase in curvature; total arthroplasty of hips and knees in relatively young adults to decrease pain and increase mobility; treatment of cystic ear swelling is conservative. Prevention of Primary Manifestations: Physical therapy may prevent early joint contractures. 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. Other: Undertake orthopedic surgery with caution as deformities tend to recur. GENETIC COUNSELING: DTD is inherited in an autosomal recessive manner. At conception, each sib of a proband with DTD has 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. The unaffected sibs of a proband have a 2/3 chance of being heterozygotes. Prenatal diagnosis for pregnancies at increased risk is possible if both disease-causing alleles of an affected family member have been identified. Ultrasound examination early in pregnancy is a reasonable complement or alternative to prenatal diagnosis by molecular genetic testing