Information on the following diseases can be found in the Related Disorders section of this report:

• Ectopia Lentis
• Ectopia Lentis (General)

The symptoms and findings associated with Weill-Marchesani syndrome may be variable from case to case, including among affected family members. However, many individuals with the disorder have an unusually short, stocky build (pyknic habitus or brachymorphism). In addition, many may have characteristic abnormalities of the skull and facial (craniofacial) area, such as an unusually short, broad head (brachycephaly) as well as small, shallow eye cavities (orbits); a pug nose; and a depressed nasal bridge. Additional craniofacial abnormities may include a narrow roof of the mouth (palate); a small, underdeveloped upper jaw (maxillary hypoplasia); and/or malformation and misalignment of certain teeth.

Many individuals with Weill-Marchesani syndrome also have distinctive malformations of the hands. For example, bones within the middle regions of the hands (metacarpals) and the fingers (phalanges) may be abnormally short (brachydactyly). The feet may also appear unusually short and wide. In addition, some individuals may develop progressive stiffness of certain joints, particularly those of the hands. In some instances, carpal tunnel syndrome may also become apparent during adolescence or adulthood. This condition is characterized by numbness, tingling, and pain of certain fingers, the thumb, and part of the palm. In some cases, burning or tingling sensations may extend to the elbow and shoulder.

Weill-Marchesani syndrome is also characterized by distinctive eye (ocular) abnormalities. Affected individuals typically have unusually small, round lenses of the eyes (spherophakia), with partial or complete absence of certain fibers (zonula ciliaris) that normally help to hold the lenses in place. As a result, some individuals with the disorder may be prone to developing progressive dislocation of the lenses (ectopia lentis) or may have the condition at birth (congenital ectopia lentis). Ectopia lentis may be characterized by shifting or tilting (i.e., partial displacement or subluxation) or complete dislocation (luxation) of the lenses, resulting in blurring of vision, double vision (diplopia), and/or quivering movements of the colored regions of the eyes (iridodonesis). Additional ocular abnormalities may also be associated with Weill-Marchesani syndrome. These may include loss of transparency of the lenses of the eyes (cataracts); abnormal shallowness of the chambers (i.e., anterior chambers) in front of the colored regions of the eye (irides) that contain the thin, watery fluid known as aqueous humor; and/or secondary glaucoma. The latter is a condition characterized by abnormally increased pressure of the fluid of the eye. Individuals with Weill-Marchesani syndrome may have varying degrees of visual impairment, including reduced clearness and clarity of vision (acuity), marked nearsightedness (myopia), or blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.

In rare instances, affected individuals may have additional physical abnormalities. For example, there has been one reported case in which the disorder was associated with a heart defect characterized by abnormal narrowing of the aortic valve (aortic stenosis). The aortic valve is the heart valve between the lower left chamber of the heart (ventricle) and the major artery (i.e., aorta) that transports oxygen-rich blood to most of the body.

Some individuals who carry a single copy of a recessive disease gene for Weill-Marchesani syndrome (heterozygous carriers) may have certain symptoms associated with the disorder. For example, such individuals may have short stature without other primary symptoms of the disorder. (For further information, please see the "Causes" section of this report below.)
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In some instances, Weill-Marchesani syndrome (WMS) is thought to be inherited as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

The parents of some individuals with Weill-Marchesani syndrome have been closely related by blood (consanguineous). In recessive disorders, if both parents carry the same gene for the same disease trait, there is an increased risk that their children may inherit the two genes necessary for development of the disease.

According to some reports, there may be partial expression of Weill-Marchesani syndrome in individuals who inherit one copy of an autosomal recessive disease gene for WMS (heterozygous carriers). More specifically, partial expression may be manifested by the presence of short stature. An individual who is a heterozygous carrier for a particular trait has inherited a gene for the trait from one parent and the alternative gene from the other parent. Heterozygosity for an autosomal recessive disorder may result in no associated symptoms (asymptomatic) or milder, more variable symptoms than seen in those with full expression of the disease. The children of an individual who is heterozygous for a particular genetic disorder will have a 50 percent risk of inheriting the gene associated with the trait in question.

In some affected families (kindreds), Weill-Marchesani syndrome has appeared to have autosomal dominant or "pseudodominant" inheritance. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

In "pseudodominance" (quasidominance), an autosomal recessive disorder appears to have autosomal dominant inheritance. More specifically, there is transmission of the trait from parent to child due to the fact that one affected parent has two copies of the disease gene whereas the other parent has one copy of the mutated gene (i.e., heterozygous carrier). As a result, the percentage of affected children more closely resembles that of an autosomal dominant rather than an autosomal recessive disorder.

Some researchers also indicate that Weill-Marchesani syndrome may result from changes (mutations) of different disease genes (genetic heterogeneity) that may be transmitted as autosomal dominant or recessive traits. Further research is needed to learn more about the underlying genetic cause or causes of Weill-Marchesani syndrome.
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Weill-Marchesani syndrome appears to affect males and females in equal numbers. The disorder was originally described in the 1930s (G. Weill, O. Marchesani). Over 30 cases have been recorded in the medical literature. Due to the variability of symptoms and the fact that some individuals may have few associated findings (e.g., short stature), researchers indicate that the disorder may be underdiagnosed. Therefore, it is difficult to determine the frequency of Weill-Marchesani syndrome in the general population.
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Symptoms of the following disorders may be similar to those of Weill-Marchesani syndrome. Comparisons may be useful for a differential diagnosis:

Ectopia lentis is an eye (ocular) abnormality characterized by shifting or tilting (i.e., partial displacement) or complete displacement of the lens of the eye. The condition may be present at birth (congenital), be progressive, or occur due to trauma. In those with ectopia lentis, associated symptoms and findings may include blurring of vision, double vision (diplopia), and unusual, quivering movements of the iris (iridodonesis). In some instances, ectopia lentis may be a hereditary condition that occurs as an isolated finding (simple ectopia lentis). In such cases, the condition may be present at birth or develop later during life. Simple ectopia lentis is usually inherited as an autosomal dominant trait. In addition to Weill-Marchesani syndrome, ectopia lentis may also occur in association with other underlying genetic disorders, including Marfan syndrome, a connective tissue disorder, and homocystinuria, a metabolic disorder. (For further information on these disorders, choose "Marfan" or "homocystinuria" as your search terms in the Rare Disease Database.)

Additional disorders may be characterized by ectopia lentis, additional ocular abnormalities, short stature, skeletal malformations, and/or other symptoms and findings similar to those potentially associated with Weill-Marchesani syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Diagnosis
In some instances, such as in families with members previously diagnosed with the disorder, Weill-Marchesani syndrome (WMS) may be suspected at birth. More commonly, the disorder is recognized during childhood, based upon detection of eye (ocular) abnormalities, potentially in association with other findings associated with the disorder. Family members of an individual diagnosed with WMS should undergo screening to detect any symptoms or findings (e.g., short stature, ocular abnormalities) that may be associated with Weill-Marchesani syndrome or heterozygosity for the disorder. (For further information on heterozygosity, please see the "Causes" section of this report above.)

The diagnosis of Weill-Marchesani syndrome may be made based upon a thorough clinical examination, a complete patient and family history, identification of characteristic physical findings, and a variety of specialized tests. These typically include ocular examinations, such as ophthalmoscopy, or the use of an instrument to view the inside of the eyes; techniques to measure pressure within the eyes (e.g., tonometry); visual field testing; and/or other ocular techniques. In addition, advanced imaging techniques (e.g., computed tomography [CT] scanning or magnetic resonance imaging [MRI]) or other diagnostic tests may be conducted to detect and characterize skeletal or other abnormalities that may be associated with the disorder. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. During MRI, a magnetic field and radio waves create detailed cross-sectional images of certain organs and tissues.

Treatment
The treatment of Weill-Marchesani syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; eye specialists (e.g., ophthalmologists and optometrists); physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); and/or other health care professionals.

Specific therapies for Weill-Marchesani syndrome are symptomatic and supportive. Experts indicate that early diagnosis of ocular abnormalities may be important in helping to ensure optimal visual development. In some cases, corrective glasses, other visual aids, and/or surgery may be recommended to help improve vision. In addition, for those with increasing fluid pressure in the eyes or glaucoma, treatment may include measures to help control pressure within the eyes (intraocular pressure), such as therapy with medicated eye drops; laser therapy to create a hole in the colored region of the eye (laser iridectomy) or surgical removal of part of the iris (iridotomy); removal of the lens; and/or other techniques.

Experts indicate the stimulating contraction (miosis) of the pupils may induce glaucoma in some affected individuals. Therefore, therapy with medications that cause the pupils to contract must be avoided (i.e., are contraindicated).

Genetic counseling will be of benefit for individuals with Weill-Marchesani syndrome and their families. Other treatment for this disorder is symptomatic and supportive.
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Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.

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