Recessive multiple epiphyseal dysplasia – Clinical characteristics caused by rare compound heterozygous SLC26A2 genotypes

Abstract Pathogenic sequence variants in the solute carrier family26 member 2 ( SLC26A2) gene result in lethal ( achondrogenesisIb and atelosteogenesis II) and non-lethal ( diastrophic dysplasiaand recessive multiple epiphyseal dysplasia, rMED) chondrodysplasias. We report on two new patients with rMED and very rare compound heterozygous mutation combinations in non- consanguineousfamilies. Patient I presented in childhood with waddling gaitand joint stiffness. Radiographs showed epiphyseal changes, bilateral coxa plana–deformity and knee valgus deformity, for which he underwent surgeries. At present 33 years his height is 165 cm. Patient II presented with cleft palate, small jaw, short limbs, underdevelopedthumbs and on radiographs, cervical kyphosiswith an underdevelopedC4. He also developed severe scoliosis but has grown at −2.9 SD curve. Molecular analysis revealed that patient I is heterozygous for two known pathogenic variants in SLC26A2, a splice site variant c.-26+2T > C and a missense variant c.1957T > A (p.Cys653Ser), while patient II is compound heterozygous for missense variants c.835C > T (p.Arg279Trp) and c.1535C > A (p.Thr512Lys). These patients further elucidate the variability of the phenotypic and genetic presentations of rMED.