Dyssegmental dysplasia Silverman–Handmaker type

Dyssegmental dysplasia, Silverman–Handmaker type is a rare genetic disorder characterized by severe skeletal abnormalities. This condition falls under the broader category of osteochondrodysplasia, which encompasses disorders related to the development of bone and cartilage. Dyssegmental dysplasia, Silverman–Handmaker type, is particularly noted for its impact on the growth and structure of the individual's bones, leading to significant physical complications and challenges.

Etiology

The disorder is caused by mutations in the HSPG2 gene, which encodes the protein perlecan. Perlecan is crucial for the normal development of cartilage and the integrity of basement membranes, which are essential components of various tissues. The mutations lead to a deficiency or malfunctioning of perlecan, disrupting the normal bone growth and cartilage development process.

Pathophysiology

In dyssegmental dysplasia, Silverman–Handmaker type, the disruption in the function of perlecan affects the formation of the bone structure, particularly in the vertebrae and long bones. The vertebrae may show irregular segmentation and fusion, while the long bones exhibit a "dumbbell" shape due to abnormal growth patterns. These skeletal abnormalities are the hallmark of the disease and are critical for diagnosis.

Clinical Features

Individuals with this condition present with a variety of symptoms, including:

• Short stature, often noticeable at birth
• Short neck and trunk
• Limited range of motion in joints
• Facial abnormalities such as a flat face, prominent eyes, and low-set ears
• Respiratory difficulties due to underdeveloped rib cage

The severity of symptoms can vary, but the condition is typically severe and, in many cases, life-threatening in infancy or early childhood due to respiratory complications.

Diagnosis

Diagnosis of dyssegmental dysplasia, Silverman–Handmaker type, is primarily based on clinical examination and radiographic findings. Prenatal ultrasound may reveal some characteristic features of the disorder, such as shortened limbs and abnormal bone development. Genetic testing can confirm the diagnosis by identifying mutations in the HSPG2 gene.

Treatment

There is no cure for dyssegmental dysplasia, Silverman–Handmaker type. Treatment focuses on managing symptoms and improving the quality of life. This may include:

• Orthopedic interventions to address skeletal abnormalities
• Respiratory support for those with chest wall and lung underdevelopment
• Physical therapy to enhance mobility and reduce joint stiffness

Prognosis

The prognosis for individuals with dyssegmental dysplasia, Silverman–Handmaker type is generally poor, with many affected infants experiencing life-threatening complications early in life. The severity of skeletal and respiratory issues largely determines the outcome.

See Also

• Osteochondrodysplasia
• Genetic disorder
• Bone dysplasia

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