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Diastrophic Dysplasia, Genetic Testing

Diastrophic dysplasia is a rare genetic disorder that primarily affects the development of the bones and cartilage. It is classified as a type of skeletal dysplasia, a group of conditions characterized by abnormal bone and cartilage growth. Diastrophic dysplasia specifically falls under the subgroup of disorders known as the short rib-polydactyly syndromes. Its overall prevalence is estimated at 1 case per 100,000 individuals. Although it is present in almost all populations, it is more prevalent in the Finnish population, where most cases have been identified.

Diastrophic dysplasia genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).

Some key features and characteristics of diastrophic dysplasia are:

  • Short Stature: Individuals with diastrophic dysplasia typically have short stature due to the abnormal development of the bones.
  • Joint Deformities: Joint deformities are common, and individuals may experience problems with their knees, hips, and other joints. Clubfoot and hand deformities are also possible.
  • Facial Features: People with diastrophic dysplasia may have distinct facial features, including a flat, broad nasal bridge, a small, upturned nose, and ears often described as cauliflower-shaped.
  • Scoliosis: Spinal abnormalities such as scoliosis (curvature of the spine) can occur in individuals with diastrophic dysplasia.
  • Polydactyly: Some individuals may have extra fingers or toes (polydactyly), though this feature is not always present.
  • Ear and Hearing Issues: Ear abnormalities and hearing loss are common in individuals with diastrophic dysplasia.
  • Cleft Palate: A cleft palate, a condition with an opening or gap in the roof of the mouth, can be associated with this disorder.
  • Joint Pain: Individuals with diastrophic dysplasia may experience joint pain and stiffness, impacting mobility.

Management of diastrophic dysplasia involves a multidisciplinary approach, including orthopedic care, physical therapy, and, in some cases, surgical interventions to address skeletal and joint issues. Genetic counseling may also be offered to families to understand the risk of recurrence in future pregnancies. The severity of symptoms can vary among individuals with diastrophic dysplasia. Early intervention and supportive care can help improve the quality of life for affected individuals.

Diastrophic dysplasia is caused by pathogenic variants in the SLC26A2 gene, which is highly expressed in cartilage and codes for a transmembrane protein that transports sulfate in cartilage cells or chondrocytes. Sulfate transport in chondrocytes is essential to maintain adequate sulfation of proteoglycans, which are components of the extracellular matrix produced by the chondrocytes themselves and which retain water, maintaining the consistency of cartilage tissue. Alteration of sulfate transporter activity causes depletion of intracellular sulfate, leading to insufficiently sulfated proteoglycans. The inheritance pattern is usually autosomal recessive, meaning both parents must carry a mutated gene for a child to be affected.

The most common pathogenic variants in the SCL26A2 gene are c.835C>T, c.532C>T, c.1957T>A, and c.-26+2T>C (IVS1+2T>C), accounting for approximately 70% of all pathogenic alleles. Of these four variants, c.835C>T is the most common. The c.-26+2T>C variant accounts for 8% of the pathogenic alleles and is the predominant variant in the Finnish population. It has been observed that 90% of the cases of diastrophic dysplasia in Finland are carriers of c.-26+2T>C. The disease can occur when a person has two copies of the same pathogenic variant in SCL26A2 (e.g., two copies of c.-26+2T>C) and also when carrying one copy of two different pathogenic variants in SCL26A2 (e.g., one copy of c.835C>T together with one copy of c.-26+2T>C resulting in a moderate disease manifestation).

The genetic test of diastrophic dysplasia analyzes the four most frequent pathogenic mutations of the SCL26A2 gene.

With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).

Additional information
Results Time4 - 5 Weeks
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