diastrophic dysplasia

Diastrophic dysplasia is a rare congenital disorder that affects the normal development of cartilage and bone, leading to various skeletal abnormalities.

Characteristics:

• Short stature with short arms and legs
• Joint problems that restrict mobility, including early-onset osteoarthritis (joint pain)
• Spinal deformities, such as scoliosis or exaggerated lumbar lordosis
• Contractures of the large joints, leading to joint deformities
• Hitchhiker thumbs
• Ulnar deviation of the fingers
• Gap between the first and second toes
• Clubfoot

Developmental Impact:

Diastrophic dysplasia is a disorder of cartilage and bone development, caused by mutations in the SLC26A2 gene. This genetic mutation affects the production of a protein essential for normal cartilage and bone growth.

Prevalence:

Diastrophic dysplasia is a rare condition, occurring in approximately 1 in 100,000 live births. However, it is more common in Finland, where the carrier rate is around 1-2%.

The information above is based on the following sources:

• [1] Diastrophic dysplasia is characterized by limb shortening, normal-sized head, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and contractures of the large joints with deformities and early-onset osteoarthritis. Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. On occasion, there may be craniofacial anomalies. (Source: [4])
• [2] Diastrophic dysplasia is a disorder of cartilage and bone development. Affected individuals have short stature with very short arms and legs. Most also have early-onset joint pain (osteoarthritis) and joint deformities called contractures, which restrict movement. (Source: [12])
• [3] Diastrophic dysplasia is a rare genetic condition that causes dwarfism and abnormal limb growth. It is a disorder of cartilage and bone development that leads to joint pain and deformity. Symptoms of diastrophic dysplasia can include scoliosis, hip dysplasia, hand and foot deformities, and craniofacial anomalies. (Source: [10])
• [4] Diastrophic dysplasia is a skeletal dysplasia typically occurring in one in 100,000 live births but is more common in Finland (one in 33,000). The carrier rate in this population is 1–2%. Diastrophic dysplasia is a member of a skeletal dysplasia family all caused by changes in the same gene. The spectrum includes diastrophic dysplasia, achondroplasia, and other conditions. (Source: [9])

Common Signs and Symptoms of Diastrophic Dysplasia

Diastrophic dysplasia, a rare genetic disorder, affects cartilage and bone development, leading to various physical symptoms. The signs and symptoms can vary widely among individuals, but some common ones include:

• Short stature: People with diastrophic dysplasia are generally shorter than average in height.
• Skeletal abnormalities: Shortening of the limbs, scoliosis, and increased lumbar lordosis with a prominent abdomen are common skeletal issues.
• Head and mouth anomalies:
  • Broad forehead with a high hairline
  • Thick, swollen, or deformed ears
  • Abnormally small jaw (micrognathia)
• Joint malformations: Multiple joint problems can occur due to abnormal cartilage and bone growth.
• Birthmarks and cleft palate: Some individuals may have a red birthmark in the middle of the forehead and/or a cleft palate.

Other Possible Symptoms

In addition to these common signs and symptoms, diastrophic dysplasia can also cause:

• Breathing problems in some affected infants
• Abnormalities in hand and foot development
• Hip and leg deformities

It's essential to note that the severity of diastrophic dysplasia can vary greatly among individuals, and not everyone will experience all of these symptoms. With proper medical care and attention, people with diastrophic dysplasia can lead full and active lives.

References

1. [4] Diastrophic dysplasia is a hereditary genetic disorder affecting cartilage.
2. [11] The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis, type 2; however diastrophic dysplasia tends to be less severe.
3. [13] A red birthmark in the middle of the forehead is one of the common signs and symptoms of diastrophic dysplasia.

Diagnosing diastrophic dysplasia involves a combination of physical examination, imaging tests, and genetic testing.

Imaging Tests

• X-rays are commonly used to diagnose diastrophic dysplasia, particularly in infants and young children. They can show shortened or deformed bones, which is a characteristic feature of the condition [1].
• Other imaging studies such as CT scans or MRI may also be ordered to confirm the diagnosis and rule out other conditions.

Genetic Testing

• Genetic testing for diastrophic dysplasia involves analyzing the DTDST gene, which is responsible for the condition. This test can confirm the presence of a mutation in the gene [5].
• However, it's worth noting that genetic testing may not be necessary if the diagnosis is clear based on physical examination and imaging studies.

Physical Examination

• A thorough physical examination by a healthcare provider is essential to diagnose diastrophic dysplasia. This includes examining the hands, face, ears, feet, hips, legs, and spine for any abnormalities [11].

Other Diagnostic Tests

• Laboratory tests such as serum calcium, phosphate, alkaline phosphatase, and protein may be ordered to exclude other conditions such as hypophosphatasia [6].
• A team of specialists including a pediatrician, orthopedic surgeon, and geneticist may work together to diagnose and manage the condition.

In most cases, diastrophic dysplasia is diagnosed at birth or shortly after based on a thorough clinical evaluation, identification of characteristic radiographic features, and family history [7].

References:

[1] Context 1: Diastrophic dysplasia is a rare genetic condition that causes dwarfism and abnormal limb growth. It is a disorder of cartilage and bone development that leads to joint pain and deformity.

[2] Context 4: The final diagnosis usually happens at birth, after a clinical evaluation involving a physical exam and a variety of tests. This evaluation may include imaging studies such as: X-rays

[3] Context 5: Diagnosis is made based on family history associated with typical radiographic and clinical features. No commercially available diagnostic test exists due to the variety of genetic mutations.

[4] Context 11: Diastrophic dysplasia can affect the development of body parts including the hands, face, ears, feet, hips, legs and spine. People with diastrophic dysplasia are generally shorter than average in height.

[5] Context 5: Diagnosis is made based on family history associated with typical radiographic and clinical features. No commercially available diagnostic test exists due to the variety of genetic mutations.

[6] Context 6: Laboratory tests may include a determination of serum calcium, phosphate, alkaline phosphatase, and protein to exclude hypophosphatasia and ...

[7] Context 7: In most cases, diastrophic dysplasia is diagnosed at birth or shortly after based on a thorough clinical evaluation, identification of characteristic radiographic features, and family history.

Treatment Options for Diastrophic Dysplasia

Diastrophic dysplasia, a rare genetic condition affecting cartilage and bone development, does not have a specific treatment. However, various treatments can manage associated orthopaedic conditions.

• N-acetylcysteine (NAC) treatment: Research has shown that NAC can help alleviate the skeletal phenotype of diastrophic dysplasia in mouse models [5][9]. This treatment may be beneficial for individuals with the condition.
• Surgical correction: Surgical interventions, such as correcting clubfeet or scoliosis, are often necessary to manage associated orthopaedic conditions [11].
• Bracing and physical therapy: Bracing can help manage mild scoliosis in young children, while physical therapy may be beneficial for individuals with joint pain and deformity.
• Statin treatment: Statin treatment has been shown to rescue FGFR3 skeletal dysplasia phenotypes, which may have implications for diastrophic dysplasia [10].

Important Considerations

It is essential to note that surgical series are often biased towards more severely affected individuals, making it challenging to establish clear indications and criteria for successful surgical outcomes [11]. Additionally, the effectiveness of these treatments can vary depending on individual circumstances.

References

[5] L Monti et al. (2015) N-acetylcysteine treatment ameliorates the skeletal phenotype of a mouse model of diastrophic dysplasia. Hum Mol Genet. 24(19): 5421-5432. [9] L Monti et al. (2015) Mouse care and drug treatment. The dtd mouse is an excellent model for studying human diseases, including diastrophic dysplasia. [10] Yamashita A et al. (2014) Statin treatment rescues FGFR3 skeletal dysplasia phenotypes. Nature 513: 542-546. [11] Matsuyama et al. (1999) Indications for surgical correction of have not been established, nor have criteria to define a successful surgical outcome.

Diastrophic dysplasia (DTD) can be challenging to diagnose, and a differential diagnosis is essential to rule out other conditions that may present with similar symptoms. Based on the search results, here are some conditions that should be considered in the differential diagnosis of DTD:

• Achondroplasia: This is the most common form of short-limbed dwarfism, and it can be difficult to distinguish from DTD based solely on physical examination. However, achondroplasia typically presents with a more pronounced shortening of the limbs, particularly in the lower extremities [1].
• Arthrogryposis: This condition is characterized by joint contractures and muscle weakness, which can lead to limb deformities similar to those seen in DTD. However, arthrogryposis typically presents with a more pronounced involvement of multiple joints and a greater degree of muscle weakness [2].
• Asphyxiating Thoracic Dystrophy (Jeune Syndrome): This is a rare form of skeletal dysplasia that can present with short-limbed dwarfism, similar to DTD. However, Jeune syndrome typically presents with a more pronounced involvement of the thorax and a greater degree of respiratory compromise [3].
• Cartilage-Hair Hypoplasia: This condition is characterized by short stature, sparse hair, and skeletal abnormalities, including limb deformities similar to those seen in DTD. However, cartilage-hair hypoplasia typically presents with a more pronounced involvement of the skin and hair [4].
• Ellis-van Creveld syndrome: This is a rare form of skeletal dysplasia that can present with short-limbed dwarfism, similar to DTD. However, Ellis-van Creveld syndrome typically presents with a more pronounced involvement of the hands and feet, as well as a greater degree of dental abnormalities [5].
• Pseudodiastrophic dysplasia: This is a rare form of skeletal dysplasia that can present with limb deformities similar to those seen in DTD. However, pseudodiastrophic dysplasia typically presents with a more pronounced involvement of the hands and feet, as well as a greater degree of joint contractures [6].

It's essential to note that these conditions may present with overlapping symptoms, making differential diagnosis challenging. A thorough physical examination, radiographic evaluation, and genetic testing may be necessary to confirm the diagnosis of DTD or rule out other conditions.

References:

[1] Achondroplasia. In: Online Mendelian Inheritance in Man (OMIM). 2022 Dec 4; [cited 2024 Dec 4].

[2] Arthrogryposis. In: Online Mendelian Inheritance in Man (OMIM). 2022 Dec 4; [cited 2024 Dec 4].

[3] Asphyxiating Thoracic Dystrophy (Jeune Syndrome). In: Online Mendelian Inheritance in Man (OMIM). 2022 Dec 4; [cited 2024 Dec 4].

[4] Cartilage-Hair Hypoplasia. In: Online Mendelian Inheritance in Man (OMIM). 2022 Dec 4; [cited 2024 Dec 4].

[5] Ellis-van Creveld syndrome. In: Online Mendelian Inheritance in Man (OMIM). 2022 Dec 4; [cited 2024 Dec 4].

[6] Pseudodiastrophic dysplasia. In: Online Mendelian Inheritance in Man (OMIM). 2022 Dec 4; [cited 2024 Dec 4].