Clinical, genetic, and orthopedic characteristics of large group of patients with diastrophic dysplasia

BACKGROUND: Diastrophic dysplasia (OMIM #222600) is a rare congenital autosomal recessive skeletal dysplasia associated with homozygous or compound-heterozygous variants in the sulfate transporter gene SLC26A2. Clinical and radiological descriptions of diastrophic dysplasia in patients of different ages will help improve the diagnosis and orthopedic treatment. AIM: To describe clinical and genetic characteristics of Russian patients with diastrophic dysplasia caused by previously described and newly identified pathogenic SLC26A2 variants. MATERIALS AND METHODS: A comprehensive examination of 28 Russian patients from 28 unrelated families aged 3 months to 34 years with clinical and radiological signs of diastrophic dysplasia was performed. To confirm the diagnosis, genealogical analysis, clinical examination, radiography, and targeted research of SLC26A2 using direct Sanger sequencing were performed. RESULTS: Typical clinical and radiological signs sufficient for diagnosing diastrophic dysplasia in newborns have been identified, which included rhizo/mesomelic shortening of the upper and lower extremities, congenital clubfoot, hand anomalies, multiple dislocations, and joint contractures. In our patients, 14 SLC26A2 variants were identified, 9 of which were first discovered. The most common variant identified in Russian patients with diastrophic dysplasia was c.1957TA (p.Cys653Ser), which accounted for 50% of the alleles. CONCLUSIONS: Clinical and genetic analyses of Russian patients with diastrophic dysplasia made it possible to identify the core clinical and radiological signs and evaluate the polymorphism of the clinical manifestations of the disease. In contrast to previously examined patients from European populations (including Finland with the largest number of patients with diastrophic dysplasia), 50% of the cases in the Russian population are caused by the c.1957TA (p.Cys653Ser) homozygous or compound-heterozygous variant.