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Diastrophic dysplasia
This condition leads to characteristic skeletal features, including short stature, limb abnormalities, and joint issues. It affects individuals from birth and is caused by changes in the SLC26A2 gene.
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Overview
Diastrophic dysplasia is a rare, inherited condition that impacts skeletal development, meaning it affects how bones and cartilage grow. It is present from birth, and its signs and symptoms vary among affected individuals [PMID:31536484]. The term 'diastrophic' refers to the twisted or distorted appearance often seen in the bones and joints.
This condition is one of a group of disorders known as chondrodysplasias, which are characterised by issues with cartilage formation. Cartilage is an important tissue that forms much of the skeleton during early development and covers the ends of bones, allowing joints to move smoothly.
Symptoms & clinical features
Individuals with diastrophic dysplasia typically present with short stature, often noticeable at birth, and disproportionately short limbs [PMID:31536484]. A common feature is clubfoot, where the foot is twisted inward and downward. Other limb abnormalities may include joint contractures, which limit the range of movement, particularly in the hands and feet, and distinctive 'hitchhiker's thumb' due to an unusual angle of the thumb.
Spinal curvature, such as scoliosis (sideways curve) or kyphosis (outward curve), is often observed and may worsen over time. Facial features can include a cleft palate (an opening in the roof of the mouth) and a small jaw. Cysts in the outer ear cartilage are also quite common early in life, which may later calcify and shrink. Breathing difficulties can occur in some infants due to a small chest cavity or airway narrowing, which may require medical attention.
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Affected organs
The primary organs and systems affected in diastrophic dysplasia are the skeletal system, including bones, cartilage, and joints. This leads to widespread skeletal changes, particularly in the limbs and spine. The respiratory system can also be indirectly affected due to changes in the chest wall and potential airway narrowing, especially in infancy.
While the condition is mainly skeletal, the ear cartilage can form cysts, and a cleft palate can affect feeding and speech. These features are all linked to the underlying issue with cartilage development throughout the body.
Risks & severity
Diastrophic dysplasia presents with a spectrum of severity, even within the same family. Complications can arise from the characteristic skeletal issues. Spinal problems, such as severe scoliosis, may require surgical intervention to prevent further progression and potential neurological impact. Joint contractures can significantly affect mobility and require ongoing management.
In infancy, there can be a risk of breathing difficulties, especially if the chest is very small or if there is airway involvement. However, with appropriate medical care, most individuals with diastrophic dysplasia have a normal life expectancy. Ongoing surveillance for spinal issues and joint function is typically part of managing the condition throughout life.
Genetic causes
Diastrophic dysplasia is caused by genetic changes (variants) in the SLC26A2 gene [PMID:10091892]. This gene provides instructions for making a protein called a sulphate transporter, which is found in cells throughout the body, particularly in cartilage-forming cells. The sulphate transporter plays a crucial role in bringing sulphate into chondrocytes, which are cells responsible for forming cartilage.
Sulphate is essential for the normal formation and function of proteoglycans, key components of cartilage. These proteoglycans give cartilage its characteristic structure and elasticity. When the SLC26A2 gene has a pathogenic variant, the sulphate transporter protein may not work correctly or may be absent. This leads to insufficient sulphate within cartilage cells, impairing the normal development and maintenance of cartilage and bone. The resulting abnormal cartilage affects skeletal growth and joint function, leading to the features seen in diastrophic dysplasia [PMID:10787556].
- SLC26A2 solute carrier family 26 member 2The SLC26A2 gene provides instructions for a protein critical in transporting sulphate ions, which is essential for the healthy development of cartilage and bone.
Inheritance pattern
Diastrophic dysplasia has an autosomal recessive inheritance pattern. This means that a person must inherit two altered copies of the SLC26A2 gene - one from each parent - to develop the condition. If a person inherits only one altered copy and one typical copy, they are considered a carrier. Carriers usually do not exhibit symptoms of the condition themselves but can pass the altered gene copy on to their children.
If both parents are carriers, there is a 1 in 4 (25%) chance with each pregnancy for their child to inherit two altered gene copies and develop diastrophic dysplasia. There is also a 2 in 4 (50%) chance for the child to be a carrier, and a 1 in 4 (25%) chance for the child to inherit two typical gene copies and not be a carrier or have the condition. Genetic counselling can provide detailed information and support for families regarding inheritance patterns and risks.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
The diagnosis of diastrophic dysplasia is often suspected based on characteristic clinical features observed at birth or in early infancy, such as short limbs, joint contractures, clubfoot, and ear cysts. Imaging studies, particularly X-rays, are crucial to identify the distinctive skeletal abnormalities, which can include shortened long bones, specific hand and foot changes, and spinal curvature.
Confirmation of the diagnosis is achieved through genetic testing, which looks for pathogenic variants in the SLC26A2 gene. In the UK, genetic testing can be accessed through the NHS Genomic Medicine Service (GMS) following a referral from a clinician, such as a paediatrician or clinical geneticist. This type of testing falls under the rare disease pathway within the GMS (NHS R-codes can be found in the National Genomic Test Directory). Genetic counselling is typically offered as part of the diagnostic process to discuss the implications of testing and inheritance.
Management & lifestyle
Management of diastrophic dysplasia aims to address the specific symptoms and improve quality of life, as there is currently no cure for the underlying genetic cause. Care is often provided by a multidisciplinary team, potentially including orthopaedic surgeons, physiotherapists, occupational therapists, geneticists, and paediatricians.
Orthopaedic interventions may involve surgery to correct clubfoot, manage joint contractures, or address spinal curvature like scoliosis. Physiotherapy and occupational therapy are vital for maintaining joint mobility, strengthening muscles, and adapting activities to enhance independence. In infancy, monitoring for breathing difficulties and ensuring adequate airway support may be necessary. Regular follow-up appointments are important to monitor skeletal development, manage new symptoms, and provide ongoing support. Genetic counselling remains available to affected individuals and their families throughout their lives.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like diastrophic dysplasia typically enter the NHS Genomic Medicine Service (GMS) pathway. This usually begins with a referral from a specialist, such as a paediatrician or orthopaedic consultant, to a clinical genetics service. Genetic counsellors play a key role in explaining the condition, inheritance patterns, and the implications of genetic testing.
Diagnostic testing for diastrophic dysplasia by analysing the SLC26A2 gene is available through the GMS, listed in the National Genomic Test Directory under specific NHS R-codes for skeletal dysplasias. If a diagnosis is confirmed, care is managed through a coordinated approach, often involving specialists at regional centres with expertise in rare skeletal conditions. Genetic counselling is provided at various stages, including pre-test, post-test, and for family planning.
Frequently asked questions
Is diastrophic dysplasia always severe?
No, the severity of diastrophic dysplasia can vary considerably, even among individuals in the same family. Some people experience milder symptoms, while others may have more significant joint and spinal issues, and in some rare cases, severe respiratory problems in infancy.
Can diastrophic dysplasia be detected before birth?
In some cases, characteristic features of diastrophic dysplasia, such as shortened limbs or clubfoot, might be observed during prenatal ultrasound scans. If such findings are present, further investigations, including prenatal genetic testing, could be offered to confirm the diagnosis.
What kind of doctors treat diastrophic dysplasia?
A team of specialists typically manages diastrophic dysplasia. This often includes orthopaedic surgeons, paediatricians, clinical geneticists, physiotherapists, and occupational therapists. Depending on individual needs, other specialists like ear, nose, and throat (ENT) doctors or anaesthetists might also be involved.
Will individuals with diastrophic dysplasia have a normal lifespan?
With appropriate medical management and surveillance, most individuals with diastrophic dysplasia can expect to have a normal life expectancy. However, severe respiratory complications in infancy can impact this for a small number of affected individuals.
Can I have children if I have diastrophic dysplasia?
Yes, individuals with diastrophic dysplasia can have children. If you have the condition, or if you are a carrier, genetic counselling can provide detailed information about the inheritance pattern and the chances of passing the condition on to your children, which can help with family planning.
References
- Adam MP, Bick S, Mirzaa GM. Diastrophic Dysplasia. 1993. PMID: 20301524
- Adam MP, Bick S, Mirzaa GM. SLC26A2-Related Atelosteogenesis. 1993. PMID: 20301493
- Campbell JW. Dysplasias in the Child's Spine. Neurosurgery clinics of North America. 2022. PMID: 36115686
- Newbury-Ecob R. Atelosteogenesis type 2. Journal of medical genetics. 1998. PMID: 9475095
- Stanescu V, Stanescu R, Maroteaux P. Pathogenic mechanisms in osteochondrodysplasias. The Journal of bone and joint surgery. American volume. 1984. PMID: 6376516
- Bondarenko M, Haiboniuk I, Solovei I. SLC26A2 Related Diastrophic Dysplasia in 42-Years Ukrainian Women. Balkan journal of medical genetics : BJMG. 2023. PMID: 37265969
- Dawson PA. Sulfate in fetal development. Seminars in cell & developmental biology. 2011. PMID: 21419855
- Baitner AC, Maurer SG, Gruen MB. The genetic basis of the osteochondrodysplasias. Journal of pediatric orthopedics. 2000. PMID: 11008738