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Abstract：
Diastrophic dysplasia (DTD) is a rare osteochondrodysplasia characterized by short-limbed short stature and joint dysplasia. DTD is caused by mutations in SLC26A2 and is particularly common in the Finnish population. However, the disease incidence in Finland and clinical features in affected individuals have not been recently explored. This registry-based study aimed to investigate the current incidence of DTD in Finland, characterize the national cohort of pediatric subjects with DTD and review the disease-related literature. Subjects with SLC26A2-related skeletal dysplasia, born between 2000 and 2020, were identified from the Skeletal dysplasia registry and from hospital patient registry and their clinical and molecular data were reviewed. Fourteen subjects were identified. Twelve of them were phenotypically classified as DTD and two, as recessive multiple epiphyseal dysplasia (rMED). From the subjects with available genetic data, 75% (9/12) were homozygous for the Finnish founder mutation c.-26+2T>C. Two subjects with rMED phenotype were compound heterozygous for p.Arg279Trp and p.Thr512Lys variants. The variable phenotypes in our cohort highlight the wide spectrum of clinical features, ranging from a very severe form of DTD to milder forms of DTD and rMED. The incidence of DTD in Finland has significantly decreased over the past decades, most likely due to increased prenatal diagnostics.
摘要：
扩张性发育不良（DTD）是一种罕见的骨软骨发育不良，其特征是身材矮小和关节发育不良。DTD是由SLC26A2中的突变引起的,并且在芬兰人群中特别常见。然而,芬兰的疾病发病率和受影响个体的临床特征最近尚未被研究。这项基于注册的研究旨在调查芬兰DTD的当前发病率，表征患有DTD的儿科受试者的国家队列并回顾疾病相关文献。SLC26A2相关骨骼发育不良的受试者，出生在2000年至2020年之间，从骨骼发育不良登记和医院患者登记中确定，并审查了他们的临床和分子数据。确定了14名受试者。其中12个被表型分类为DTD，2个被分类为DTD，作为隐性多发性骨phy发育不良（rMED）。从有遗传数据的受试者中，75％（9/12）是纯合的芬兰创始人突变c.-262T>C。具有rMED表型的两个受试者对于p.Arg279Trp和p.Thr512Lys变体是复合杂合的。我们队列中的可变表型突出了广泛的临床特征，从非常严重的DTD形式到较温和的DTD和rMED形式。在过去的几十年中，DTD在芬兰的发病率显着下降，很可能是由于产前诊断增加。
