What are the other Names for this Condition? (Also known as/Synonyms)

• Congenital Mesodermal Dysmorphic Dystrophy
• Spherophakia-Brachymorphic Syndrome
• WMS (Weill Marchesani Syndrome)

What is Weill Marchesani Syndrome? (Definition/Background Information)

• Weill Marchesani Syndrome (WMS) is a rare congenital disorder that is primarily characterized by connective tissue abnormalities in the lens of the eye
• The signs and symptoms of Weill Marchesani Syndrome, apart from eye lens issues and cataracts, may also include short stature, joint stiffness, and brachycephaly (unusually short, broad head). The possible complications of WMS include glaucoma that can result in blindness
• Weill Marchesani Syndrome is caused by the inheritance of mutated genes that either follow autosomal dominant or autosomal recessive inheritance patterns. The autosomal dominant genes of interest are the FBN1 and LTBP2 genes, and the autosomal recessive gene of interest is the ADAMTS10 gene
• Weill Marchesani Syndrome is diagnosed through ocular exams and imaging techniques. Genetic testing can be used to determine if a child has the autosomal dominant or recessive version of the disorder
• A treatment of Weill Marchesani Syndrome may involve the use of vision aids and eye surgery, as required. The prognosis of the disorder may vary from one individual to another

Who gets Weill Marchesani Syndrome? (Age and Sex Distribution)

• Weill Marchesani Syndrome is a rare congenital disorder that manifests in newborn children
• Both males and females can be affected
• Worldwide, all racial and ethnic backgrounds may be affected, and no specific preference is noted

What are the Risk Factors for Weill Marchesani Syndrome? (Predisposing Factors)

• Presently, having a positive family history of the condition is the only known risk factor for Weill Marchesani Syndrome
• No other risk factors have been identified for Weill Marchesani Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Weill Marchesani Syndrome? (Etiology)

Weill Marchesani Syndrome is caused by:

• Inheritance of mutated FBN1 and LTBP2 genes that follow an autosomal dominant pattern. Autosomal dominant inheritance only requires one mutated gene
• Inheritance of a mutated ADAMTS10 gene that follows an autosomal recessive inheritance pattern. The autosomal recessive pattern requires two mutated genes, one from each parent

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Weill Marchesani Syndrome?

The signs and symptoms of Weill Marchesani Syndrome may vary from one individual to another and may be mild or severe. It may include:

• Eye abnormalities such as:
  • Cataracts
  • Microspherophakia (altered shape of the eye lens)
  • Ectopia lentis (dislocation of the eye lens)
• Short stature and brachycephaly (unusually short and broad head)
• Joint stiffness and abnormalities of the skull and face
• Narrowed pulmonary valve (pulmonary stenosis)
• Heart abnormalities

How is Weill Marchesani Syndrome Diagnosed?

A healthcare professional can diagnose Weill Marchesani Syndrome through the following tests and procedures:

• Complete physical examination and evaluation of family medical history
• Assessment of the presenting signs and symptoms
• Ocular exams such as ophthalmoscopy tonometry and visual field testing 
• CT and MRI scans of the eye
• Other imaging studies as needed
• Assessment of heart and lung function
• Genetic testing to look for mutated genes

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Weill Marchesani Syndrome?

The complications of Weill Marchesani Syndrome may include:

• Emotional stress for the parents and caregivers
• Myopia (nearsightedness)
• Glaucoma (a group of eye conditions that cause deterioration of the optic nerve)
• Complete loss of vision
• Pulmonary valve stenosis
• Ductus arteriosus (congenital heart abnormality)
• Reduced quality of life

How is Weill Marchesani Syndrome Treated?

Presently, Weill Marchesani Syndrome is an incurable genetic condition. However, treatment interventions may be employed to relieve the associated symptoms, such as:

• Corrective glasses and visual aids 
• Ocular surgery to improve vision
• Laser therapy to reduce an increase in eye pressure (that can cause glaucoma)
• Symptomatic management of heart and lung presentations

How can Weill Marchesani Syndrome be Prevented?

Weill Marchesani Syndrome may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Weill Marchesani Syndrome? (Outcomes/Resolutions)

• The prognosis for Weill Marchesani Syndrome depends upon the severity of the associated symptoms and complications. It can vary from one child to another
• Individuals with severe ocular complications may have a poorer prognosis due to high risk of blindness

Additional and Useful Relevant Information of Weill Marchesani Syndrome:

Information on glaucoma can be found at:

https://www.dovemed.com/diseases-conditions/glaucoma/