Clinical Guidance

Genotype-phenotype correlations indicate that the amount of residual activity of the sulfate transporter modulates the phenotype in this spectrum of disorders, which extends from lethal achondrogenesis type 1B (ACG1B) to mild SLC26A2-MED. Homozygosity or compound heterozygosity for pathogenic variants predicting stop codons or structural pathogenic variants in transmembrane domains of the sulfate transporter are associated with ACG1B, while pathogenic variants located in extracellular loops, in the cytoplasmic tail of the protein, or in the regulatory 5'-flanking region of the gene result in less severe phenotypes .

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"

Diagnostic Criteria

Suggestive Findings

SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED) should be suspected in individuals with the following clinical and radiographic features.

Clinical features

• Joint pain (usually in the hips and knees). Onset of pain is variable, but usually occurs in late childhood. Some individuals have no pain.

• Deformity of hands, feet, and knees

• Scoliosis

Radiographic features

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"

Differential Diagnosis

SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED) needs to be distinguished from the more common autosomal dominant forms of multiple epiphyseal dysplasia (MED). Clinical and radiographic differences between the genetically distinct forms of these skeletal dysplasias may allow clinicians to distinguish between them . Note: In contrast to autosomal dominant MED, prepubertal children with SLC26A2-MED usually do not have short stature.

Table 3.

Autosomal Dominant Multiple Epiphyseal Dysplasia*

Gene | Clinical Features

COL9A1

| COL9A1-, COL9A2-, COL9A3-MED appear to have more severe knee involvement but relative sparing of the hips, resulting in a milder course than MED assoc w/COMP or SLC26A2 pathogenic variants.

COL9A2

COL9A3

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Height measurement

• Elicitation of pain history

• Radiographs of the entire spine (AP and lateral), pelvis (AP), and knees (AP and lateral), to determine the extent and severity of joint involvement

• Consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and implications of SLC26A2-MED to facilitate medical and personal decision making

Treatment of Manifestations

Symptomatic individuals should be seen by a physical therapist and an orthopedist to assess the possibility of treatment (physiotherapy for muscular strengthening and maintaining mobility, cautious use of analgesic medications such as nonsteroidal anti-inflammatory drugs) and the optimal time for surgery (joint replacement), if indicated. Intensive physiotherapy may delay joint contractures and help maintain mobility. Psychosocial support addressing issues of chronic pain and career counseling is warranted.

Surveillance

Radiographic surveillance by an orthopedist is appropriate.

Agents/Circumstances to Avoid

Sports involving joint overload are to be avoided.

Evaluation of Relatives at Risk

Predictive testing of at-ris...

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"

Clinical Guidance

Sports involving joint overload are to be avoided.

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"

Surveillance Guidelines

Radiographic surveillance by an orthopedist is appropriate.

Source: GeneReviews — "SLC26A2-Related Multiple Epiphyseal Dysplasia"