Introduction:
Dysplasia is a term referring to the atypical growth and development of cells or organs. Microscopically, the cells show abnormal variations in morphology and contents. The dysplasia can affect both the soft tissues at an epithelial level as well as the hard tissues like bone (fibrous dysplasia). Hip dysplasia and myelodysplastic syndrome will come under organ dysplasia on a macroscopic level.
Dysplasia is not generally cancer but is considered a precancerous condition.
What Is Diastrophic Dysplasia?
Diastrophism means deformation or distortion. Diastrophic dysplasia is a rare inherited genetic disorder that passes on in an autosomal recessive pattern (affected genes from both parents will be needed to cause the disease). The ailment predominantly affects the cartilages and bones and affects the development of hands, legs, feet, face, hip, and spine.
What Are the Causes of Diastrophic Dysplasia?
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Mutation of the SLC26A2 (sulfate transporter) gene is the main reason for the development of diastrophic dysplasia. This gene is responsible for the normal growth and conversion of cartilage into bone.
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Cartilage is a flexible precursor of bone tissue that calcifies to form hard bone, and the thin layer of cartilage continues to cover the bone ends for protection.
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Thus changes in the protein-encoding of the SLC26A2 gene will result in cartilage structure alteration and hinder proper bone formation leading to skeletal deformities typically belonging to diastrophic dysplasia.
What Are the Clinical Features of Diastrophic Dysplasia?
The following are the clinical presentations of diastrophic dysplasia.
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Limbs: The growth and development of both the hands and legs are affected and shortened. The thumb can extend or bend beyond the limit forming a Z-shaped deformity as seen in Hitchhiker’s thumbs. There is increased deviation between the fingers and the presence of clubfoot (twisted feet).
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Trunk: Shortened body size has a compressed look. The chest is visibly small, and the abdomen is distended.
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Symphalangism: Fusion of interphalangeal joints and absence of visible creases on the palm side. The fingers are always straight and unable to bend.
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Long Bones: Dislocated from their normal position as seen in the forearm (radius).
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Others: Cleft palate, ear swelling (presence of cysts), hearing loss, visual disturbances, and hemangiomas (bright right bump) on the forehead are found.
How to Diagnose Diastrophic Dysplasia?
The unique clinical and radiological findings of diastrophic dysplasia can be suggestive of the disease itself. Gene testing will always be a standard for diagnosing genetic disorders.
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Single-gene Testing: Evaluating the SLC26A2 shows alteration in the amino acid sequence, like gene pattern insertion, deletion missense, and duplications.
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Comprehensive Genomic Testing: Unlike single-gene testing, comprehensive genomic testing involves sequencing all the genes at once. It gives a generalized overview of genetic alteration without determining the specific gene involvement.
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Biopsy: A specimen of defective cartilage can be viewed under the microscope, which shows changes in the proteoglycan (core protein with carbohydrate side chains) molecules of the fiber matrix. The slide shows cystic areas with a paucity of cellular elements. There will be a disturbance in the zones of growth plates with capillary and fibrotic invasion. All these abnormalities are found in long bones of the arms and legs and in other bones where they undergo endochondral ossification (bone formed from the cartilage). At the same time, bones that develop without prior cartilage formation will not show ossification abnormalities.
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Blood Test: The blood sample can be evaluated for the levels of calcium, phosphate, alkaline phosphatase, and protein.
How to Treat Diastrophic Dysplasia?
Treatment depends on the manifestations of diastrophic dysplasia.
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Cervical Kyphosis: Cervical spine surgery is indicated in those who show symptoms of spinal cord impingement caused by cervical kyphosis.
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Contractures: It is important to maintain joint flexibility in children born with diastrophic dysplasia. This is to prevent the tightness and stiffness of the joints, which will cause pain on slight movements.
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Clubfoot: The clinical features and abnormalities of clubfoot often recur even after treatment. Extensive surgery like osteoplasty (bone reshaping) of the foot bones in addition to tenotomy (incision or excision of tendon tissues) may be required in diastrophic dysplasia.
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Scoliosis: Children presenting with scoliosis are kept under observation, and intervention is not needed unless the condition causes neurological or respiratory problems. Definitive treatment like surgery is only indicated in the post-pubertal phase.
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Premature Degenerative Arthrosis: Total arthroplasty of hips and knees will reduce pain and increase mobility in a group of adults. Arthroplasty is indicated in relatively young adults.
What Is the Differential Diagnosis for Diastrophic Dysplasia?
The other disorders that come under the SLC26A2-related skeletal disorder spectrum are,
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Achondrogenesis Type 1B: Achondrogenesis means a defect in the cartilage, thereby affecting bone formation. This condition is a severe form of skeletal disorder showing hypodysplasia (small size and malformed) of the vertebra, chest bones, and limbs.
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Atelosteogenesis Type 2: A disorder of bone and cartilage. The affected children will have short arms and legs.
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Recessive Multiple Epiphyseal Dysplasias: The abnormal skeletal development will cause pain and a change in the shape of the bone.
Some of the differential diagnoses of dystrophic dysplasia are,
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Chondrodysplasia and Abnormal Joint Development: The bones in the hands and fingers ossify (hardening) prematurely, resulting in their malformation.
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Desbuquois Dysplasia: This condition is a form of chondrodysplasia that is inherited in an autosomal recessive pattern.
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Arthrogryposis Multiplex Congenita: Various conditions with features of joint contractures or stiffness.
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XL Otopalatodigital Spectrum Disorders: Mutation in X-chromosome causing cleft palate, hearing loss, and skeletal disorders in skull and limbs.
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Larsen Syndrome or Atelosteogenesis 1 Spectrum: A congenital disorder with dislocation of large joints and face anomalies.
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Omodysplasia: An autosomal recessive disorder with skeletal deformation.
Conclusion:
Diastrophic dysplasia is a birth defect that can be fatal sometimes. But most infants survive with certain physical abnormalities. The limbs, vertebras, and large joints are affected the most. Since it is an inherited disorder, genetic counseling for the family members is necessary to keep them informed about the disease's nature and progression.
