Sulfate Transporter-Related Osteochondrodysplasia (SLC26A2)
Sulfate transporter-related osteochondrodysplasia is an autosomal recessive disease caused by pathogenic variants in the SLC26A2 gene. It is a pan-ethnic disease, but there is an increased incidence in individuals of Finnish descent due to the presence of a founder mutation. Four different bone disorders are caused by pathogenic variants in this gene, representing a continuum of severity from the mild recessive multiple epiphyseal dysplasia, to the more severe diastrophic dysplasia, to the lethal atelosteogenesis type 2 and achondrogenesis type 1B. Recessive multiple epiphyseal dysplasia is the mildest SLC26A2-related dysplasia. It is characterized by skeletal abnormalities of the spine, hands and feet and knees, and joint pain beginning in childhood. Onset may be at birth or in childhood. Final height is usually in the normal range. Diastrophic dysplasia is characterized by short stature caused by shortening of the long bones, skeletal deformities, including scoliosis, and contractures of the hips and feet (club feet). Respiratory problems are sometimes lethal in infants, but those that survive have normal intelligence and progressive skeletal abnormalities. Atelosteogenesis type 2 has clinical features similar to diastrophic dysplasia, but is more severe in that the ribs are too small to allow proper lung development, which results in death shortly after birth. Achondrogenesis type 1B is a severe skeletal disorder characterized by very short limbs and small ribs that result in lung underdevelopment, leading to death in the prenatal or newborn period. Some general genotype-phenotype correlations have been proposed, including the presence of severe disease, usually achondrogenesis type 1B, in patients with two null variants or two pathogenic variants in the transmembrane domains. Most variants can cause more than one type of SLC26A2-related dysplasia depending on the severity of the second allele.
For information about carrier frequency and residual risk, please see the residual risk table.