Rare Oncology News

Disease Profile

Weill-Marchesani syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

Q87.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

WM Syndrome; WMS; Spherophakia-brachymorphia syndrome;

Categories

Congenital and Genetic Diseases; Connective tissue diseases; Eye diseases;

Summary

Weill-Marchesani syndrome is an inherited connective tissue disorder that mainly affects the bones and eyes. People with this syndrome are usually short in height and often have short fingers and limited joint movement, especially of the hands. Weill-Marchesani syndrome also causes problems with the lens of the eye that lead to severe nearsightedness, and it can also cause glaucoma. An eye lens problem called microspherophakia is characteristic of Weill-Marchesani syndrome. Microspherophakia refers to a small, sphere-shaped lens, which is associated with nearsightedness (myopia) that worsens over time. The lens also may be positioned abnormally within the eye (ectopia lentis). Occasionally patients with this syndrome have heart defects.[1][2] In some families this syndrome is inherited in an autosomal recessive pattern and caused by mutations in the ADAMTS10 or LTBP2 genes. It can also have autosomal dominant inheritance, and in these cases is caused by a FBN1 gene mutation.[1] Treatments for Weill-Marchesani syndrome are symptomatic and supportive.[3] People with this condition usually need regular eye exams and sometimes need eye surgery.[1]

Symptoms

Signs and symptoms of Weill-Marchesani syndrome may include:[1][2]

  • Short height, but arms, legs, body, and head size are all proportionate to height: Adult height for men ranges from 4 feet, 8 inches to 5 feet, 6 inches (or 142-169 cm) and adult height for women ranges from 4 feet, 3 inches to 5 feet, 2 inches (or 130-157 cm)
  • Short fingers (brachdactyly)
  • Joint stiffness 
  • Eye problems, which are typically recognized in childhood and include small spherical lens (microspherophakia), severe nearsightedness (myopia), abnormal position of the lens (ectopia lentis), and glaucoma, all of which can result in vision loss 
  • Heart problems, such as pulmonary valve stenosis or ductus arteriosus

Usually people with Weill-Marchesani syndrome have normal intelligence.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Brachydactyly
Short fingers or toes
0001156
Glaucoma
0000501
High myopia
Severe near sightedness
Severely close sighted
Severely near sighted

[ more ]

0011003
Short stature
Decreased body height
Small stature

[ more ]

0004322
Short thumb
Short thumbs
Small thumbs

[ more ]

0009778
30%-79% of people have these symptoms
Ectopia lentis
0001083
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
5%-29% of people have these symptoms
Aortic valve stenosis
Narrowing of aortic valve
0001650
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
1%-4% of people have these symptoms
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Microspherophakia
0030961
Percent of people who have these symptoms is not available through HPO
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth

[ more ]

0006482
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Blindness
0000618
Brachycephaly
Short and broad skull
0000248
Broad metacarpals
Wide long bones of hand
0001230
Broad metatarsal
Wide long bone of foot
0001783
Broad palm
Broad hand
Broad hands
Wide palm

[ more ]

0001169
Broad phalanges of the hand
Wide hand bones
0009768
Broad ribs
Wide ribs
0000885
Broad skull
Increased width of skull
Wide skull

[ more ]

0002682
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Lumbar hyperlordosis
Excessive inward curvature of lower spine
0002938
Misalignment of teeth
Abnormal dental position
Abnormal teeth spacing
Abnormality of alignment of teeth
Abnormality of teeth spacing
Crooked teeth
Malaligned teeth
Malposition of teeth
Malpositioned teeth

[ more ]

0000692
Mitral regurgitation
0001653
Narrow palate
Narrow roof of mouth
0000189
Patent ductus arteriosus
0001643
Proportionate short stature
0003508
Scoliosis
0002650
Shallow anterior chamber
0000594
Shallow orbits
Decreased depth of eye sockets
Shallow eye sockets

[ more ]

0000586
Spinal canal stenosis
Narrow spinal canal
0003416
Thickened skin
Thick skin
0001072
Thin bony cortex
0002753
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629

Cause

Weill-Marchesani syndrome is usually caused by changes or mutations in the ADAMTS10 gene. In some cases, it can be caused by changes in the either the FBN1 gene or the LTBP2 gene.[1]

Diagnosis

The diagnosis of Weill-Marchesani syndrome is made by a doctor when a child has the characteristic signs and symptoms of the syndrome. Genetic testing can help confirm the diagnosis.[1]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Although there is no cure for Weill-Marchesani syndrome, there are treatments that can help minimize or correct many of the symptoms that do develop.[3] People with this syndrome often need a team of medical specialists, including pediatricians, eye specialists (ophthalmologists and optometrists), orthopedists, and cardiologists.[3][2]

    Regular eye exams are important for early diagnosis of eye problems. A timely diagnosis and treatment of developing eye problems is very important to increase the chance that vision loss can be minimized. Corrective glasses, visual aids, or eye surgery may be needed to improve vision. Removal of the microspherophakia is recommended to control intraocular pressure and improve vision. Increased pressure within the eye (glaucoma) may be treated with eye drops, laser therapy, surgical removal of the iris or lens. Contraction or dilation of the pupils can cause glaucoma in some people with Weill-Marchesani syndrome. Medications that contract the pupil must be avoided, and medications that dilate the pupils must be given with care.[3][2]

    Joint stiffness and bone abnormalities can cause complications if anesthesia is needed. A person with Weill-Marchesani syndrome needs to tell their doctor, surgeon, and anesthesiologist of the diagnosis before receiving anesthesia, as the syndrome can impact airway management.[3]

    Recommended evaluations when a child is first diagnosed with Weill-Marchesani syndrome include:[1] 

    • Complete eye exam by an ophthalmologist
    • Evaluation by a medical genetics specialist
    • Cardiac echocardiogram

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Genetics Home Reference (GHR) contains information on Weill-Marchesani syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            The Online Mendelian Inheritance in Man (OMIM)
            The Online Mendelian Inheritance in Man (OMIM)
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Weill-Marchesani syndrome. Click on the link to view a sample search on this topic.

            References

            1. Tsilou E & MacDonald I. Weill-Marchesani Syndrome. GeneReviews. 2013; https://www.ncbi.nlm.nih.gov/books/NBK1114/.
            2. Weill-Marchesani syndrome. Genetics Home Reference. 2015; https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome#resources.
            3. Weill-Marchesani Syndrome. National Organization for Rare Disorders (NORD). 2015; https://rarediseases.org/rare-diseases/weill-marchesani-syndrome/.
            4. Guo H, Wu X, Cai K &i Qiao Z. Weill-Marchesani syndrome with advanced glaucoma and corneal endothelial dysfunction: a case report and literature review. BMC Ophthalmology. 2015; 15:3. https://bmcophthalmol.biomedcentral.com/articles/10.1186/1471-2415-15-3.

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