SLC26A2-related disorders

What Is Sulfate Transporter-Related Osteochondrodysplasia?

Sulfate transporter-related osteochondrodysplasias are a group of inherited diseases caused by mutations in a gene called SLC26A2, which plays a role in cartilage and bone formation. These diseases include achondrogenesis type Ib, diastrophic dysplasia, atelosteogenesis type II, and recessive multiple epiphyseal dysplasia.

Achondrogenesis Type Ib (ACGIb)

ACGIb is a severe skeletal disease that is fatal either before or shortly after birth. Infants born with the disease have extremely short arms, legs, fingers, and toes. The fingers and toes may be rotated inward (clubfoot). Infants with the disease also tend to have flat faces, protruding abdomens, narrow chests, and short necks that show thickening of the soft tissue. Many are born with hernias.

Fetuses with ACGIb are often in the breech position, “upside-down,” with their feet toward the birth canal. Mothers of fetuses with ACGIb are prone to other pregnancy complications, like too much amniotic fluid (polyhydramnios).

Diastrophic Dysplasia

Diastrophic dysplasia, also called diastrophic dwarfism, causes bone and joint abnormalities. It does not typically affect intelligence or mental function.

Individuals with diastrophic dysplasia have very short arms and legs (short stature, typically between 3.2 and 4.6 feet), although their skulls are often normally sized. They are often born with bone deformities such as clubfoot, cleft palate, a curved spine, and "hitchhiker thumbs" (thumbs that are bent back). The outside of the ears may also be swollen at birth which can result in abnormal-looking ears later in life. Infants may also have a small ribcage and chest with a protruding abdomen which can lead to breathing problems.

Joint abnormalities leading to pain develop at an early age, and many individuals have difficulty moving their joints, which worsens with age. This, in turn, may make walking difficult.

Atelosteogenesis Type II

Atelosteogenesis type II is similar to diastrophic dysplasia with the main symptoms including bone deformities, cleft palate, narrow chest with protruding abdomen, and atypical facial features. The main difference between the two diseases is that atelosteogenesis type II is much more severe, with most affected individuals being stillborn or dying from respiratory failure soon after birth.

Recessive Multiple Epiphyseal Dysplasia (rMED)

rMED causes bone deformities and joint pain. Unlike individuals with the related diseases mentioned above, those with rMED typically reach normal height and live normal lifespans. Half of the individuals with rMED are born with an obvious bone abnormality such as cleft palate, clubfoot, or an inwardly-curved little finger. Some also have a mild curvature of the spine (scoliosis).

All individuals with the disease develop joint pain, often late in childhood. Pain is most common in the hips and knees but can also occur in the wrists, fingers, and elsewhere.

How Common Is Sulfate Transporter-Related Osteochondrodysplasia?

ACGIb is very rare, and its frequency is unknown. One particular mutation that causes the disease is most common in Finland, but other mutations are found globally.

Diastrophic dysplasia has been estimated to affect 1 in 100,000 people worldwide. It has been found in individuals of all ethnicities but is most common in Finland.

Atelosteogenesis type II is extremely rare, and its frequency is unknown.

rMED is also rare, but researchers believe it may be more common than realized, due to individuals with mild symptoms who go undiagnosed.

How Is Sulfate Transporter-Related Osteochondrodysplasia Treated?

There is no treatment for ACGIb or atelosteogenesis type II. Infants with either disease can only be made as comfortable as possible.

For individuals with diastrophic dysplasia, the goal of treatment is to improve and maintain mobility while relieving pain. This can be done with a combination of muscle exercises, surgery, and the use of plaster casts to hold children's joints in place. In particular, surgery can be used to correct clubfoot, to reduce compression of the spinal cord, or to correct knee joints. Surgery may need to be repeated, as bone deformities tend to re-form after surgery. It is important that individuals with diastrophic dysplasia do not become obese, as this puts harmful weight and strain on their knee and ankle joints.

rMED is usually treated through a combination of targeted muscle strengthening exercises and non-steroidal anti-inflammatory drugs (NSAIDs). Individuals with the disease should avoid sports and activities that stress their joints. Obesity can put a strain on the joints. In some circumstances, surgery may be useful.

What Is the Prognosis for an Individual with a Sulfate Transporter-Related Osteochondrodysplasia?

The prognosis for an infant with ACGIb or atelosteogenesis type II is poor. They will die before or shortly after birth.

Infants with diastrophic dysplasia rarely face life-threatening breathing problems. Most individuals with diastrophic dysplasia live into adulthood and usually have normal intelligence and mental function. All will face physical challenges with walking and other movement and may rely on various mechanical aids for mobility.

Individuals with rMED can perform most daily activities, provided these do not stress the joints. Despite joint pain and some bone and joint abnormalities, individuals with rMED can live normal, healthy lives with a normal lifespan.