Weill-Marchesani Syndrome

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Description

Weill-Marchesani Syndrome (WMS) is a rare genetic disorder characterized by distinctive features affecting the eyes and skeletal system. This syndrome impacts individuals in various ways, requiring specialized care and understanding. This blog delves into the complexities of WMS, shedding light on its causes, symptoms, diagnosis, and management.

Genes Involved

Genes Involved in Weill-Marchesani Syndrome:

• ADAMTS10: A gene responsible for encoding an enzyme that plays a crucial role in the formation of collagen, a protein essential for connective tissues.
• FBN1: A gene encoding fibrillin-1, a protein vital for the structure of elastic fibers in connective tissues.
• LTBP2: A gene that produces a protein essential for the assembly of collagen fibers.
• TGFBR2: A gene that produces a receptor for transforming growth factor beta (TGF-beta), a signaling molecule involved in connective tissue development.

Recognizing the Signs and Symptoms

Recognizing the Signs and Symptoms of Weill-Marchesani Syndrome:

• Eye Abnormalities:
  • Microspherophakia: Small, abnormally shaped lens of the eye
  • Myopia (nearsightedness): Difficulty seeing distant objects
  • Glaucoma: Increased pressure inside the eye
  • Cataracts: Clouding of the lens
• Skeletal Features:
  • Short stature: Generally shorter than average height
  • Brachydactyly: Short fingers and toes
  • Limited joint mobility: Restricted range of motion in joints
  • Kyphosis (hunchback): Abnormal curvature of the spine
  • Scoliosis (lateral curvature of the spine):
• Other Potential Symptoms:
  • Hearing loss: May occur in some cases
  • Cardiac abnormalities: Rarely, heart problems may be present
  • Dental anomalies: Unusual tooth development

Causes

Causes of Weill-Marchesani Syndrome:

Weill-Marchesani Syndrome is primarily caused by mutations in genes that are responsible for the production of proteins crucial for the development of connective tissues. These genes include:

• ADAMTS10: This gene is linked to most cases of WMS. Mutations in this gene disrupt the proper formation and function of collagen, leading to the characteristic features of the syndrome.
• FBN1: Mutations in this gene can result in a milder form of WMS, often associated with fewer skeletal abnormalities.
• LTBP2: Mutations in this gene are associated with a rare type of WMS that may also include heart defects.
• TGFBR2: Mutations in this gene can contribute to a specific form of WMS that can manifest with other health issues.

Inheritance/recurrence risk

Inheritance or Recurrence Risk of Weill-Marchesani Syndrome:

Weill-Marchesani Syndrome is typically inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated gene, one from each parent, to develop the syndrome.

If both parents carry the mutated gene, there is a 25% chance with each pregnancy that their child will inherit the syndrome.

If one parent has WMS and the other is a carrier, there is a 50% chance of their child inheriting the disorder.

However, in some cases, WMS can arise due to spontaneous mutations, meaning the gene mutation is not inherited from parents.