Chst3 related disorder (sed- Omani)

Chst3 related disorder (sed- Omani)

Overview

CHST3-related skeletal dysplasia, sometimes referred to as SED-Omani type or Spondyloepiphyseal dysplasia with congenital joint dislocations, is a genetic disorder characterized by bone and joint abnormalities. It is caused by mutations in the CHST3 gene, which encodes an enzyme involved in cartilage development. The condition is inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for their child to be affected. 

Symptoms

Short Stature: Individuals with this disorder typically have a short stature, with adults often being under 4.5 feet tall. 

Joint Dislocations: Congenital joint dislocations, particularly of the knees, hips, and elbows, are a hallmark of the condition. 

Clubfeet: An inward- or upward-turning foot (clubfoot) is also a common feature. 

Limited Range of Motion: Affected individuals may experience a reduced range of motion in large joints. 

Spinal Deformities: Progressive kyphosis (curvature of the spine) and scoliosis (lateral curvature of the spine) can develop. 

Other Features: In some cases, minor heart valve defects, tooth anomalies, and other non-skeletal complications like inguinal hernia and gastric volvulus may be present. 

Inheritance:  CHST3-related skeletal dysplasia is inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the altered gene for their child to be affected. 

Causes

CHST3 Gene and its Function:

The CHST3 gene provides instructions for making an enzyme called C6ST-1. This enzyme is crucial for the sulfation of chondroitin-containing proteoglycans, which are essential components of cartilage. 

Mutations and their Effects:

Mutations in the CHST3 gene lead to a deficiency or malfunction of the C6ST-1 enzyme, which disrupts cartilage development. 

Skeletal Dysplasia:

This disruption results in various skeletal abnormalities, including:

Short stature of prenatal onset. 

Joint dislocations, particularly in the knees, hips, and elbows. 

Club feet. 

Limited range of motion in large joints. 

Progressive spinal curvature (kyphosis). 

Occasional scoliosis. 

Minor heart valve dysplasia. 

Diagnosis

Short stature: Individuals with CHST3-related dysplasia typically have short stature from birth. 

Joint dislocations: Dislocations, particularly of the hips and knees, are a common feature. 

Clubfeet: Bilateral clubfeet are frequently observed. 

Limited range of motion: Joint stiffness and limited movement in large joints are characteristic. 

Kyphoscoliosis: Progressive curvature of the spine can develop. 

2. Radiographic Imaging:

X-rays: Radiographs reveal abnormalities in bone development, including:

Joint dislocations and malalignment. 

Epiphyseal dysplasia (abnormal growth plates). 

Metaphyseal flaring (widening of the ends of long bones). 

Changes in vertebral bodies (platyspondyly, irregular endplates). 

Wide interpedicular distance at L1. 

Spinal deformities: X-rays are used to assess the severity of kyphoscoliosis. 

3. Genetic Testing:

Biallelic CHST3 variants: CHST3-related dysplasia results from mutations in the CHST3 gene. 

Molecular testing: Genetic testing confirms the diagnosis by identifying the presence of CHST3 mutations. 

Differential diagnosis: Genetic testing helps differentiate CHST3-related dysplasia from other skeletal dysplasias. 

4. Differential Diagnosis:

Autosomal dominant Larsen syndrome: Characterized by joint dislocations and other skeletal abnormalities.

Spondyloepiphyseal dysplasia congenita (SEDC): Another type of skeletal dysplasia with joint dislocations, but typically caused by mutations in different genes.

Other skeletal dysplasias: Genetic testing can help distinguish CHST3-related dysplasia from other less common skeletal conditions. 

5. Genetic Counseling:

Autosomal recessive inheritance: CHST3-related dysplasia is inherited in an autosomal recessive manner.

Carrier testing: Family members can be tested to determine if they are carriers of the CHST3 mutation.

Prenatal testing: In families with a history of CHST3-related dysplasia, prenatal testing can be offered to determine if a fetus is affected.

Treatment

Surgical Correction:

Surgical intervention is often needed to correct joint dislocations, particularly in the hips, knees, and elbows. While surgery can improve joint function, it may not always be completely successful and multiple procedures may be required.

Orthopedic Management:

This includes bracing for scoliosis and kyphosis, and spinal fusion for severe spinal deformities.

Physical Therapy:

Physical therapy may be helpful in managing some of the effects of the disorder, but its effectiveness is limited, especially in correcting joint dislocations.

Cardiac Management:

If there are cardiac manifestations, treatment is provided by a cardiologist as needed.

Dental Management:

Dental anomalies may require treatment by a dentist.

Surveillance:

Ongoing surveillance is crucial, including regular clinical evaluations by an orthopedist experienced in skeletal dysplasia, and radiographic imaging as needed. Echocardiograms may also be required to monitor for any cardiac issues. 

Surveillance and Management:

Avoidance of High-Impact Activities:

Individuals with CHST3-related skeletal dysplasia should avoid activities that place high stress on their joints, such as jogging, and maintain a healthy weight to minimize joint stress.

Genetic Counseling:

Genetic counseling is important to understand the inheritance pattern of the condition and the risk of recurrence in future pregnancies.

Regular Follow-up:

Regular follow-up with specialists (orthopedist, cardiologist, dentist) is crucial to monitor the progression of the condition and address any emerging issues. 

Type of Doctor Department : Geneticist/Medical Geneticist , Orthopedic Surgeon