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Weill-Marchesani Syndrome

Includes: ADAMTS10-Related Weill-Marchesani Syndrome, FBN1-Related Weill-Marchesani Syndrome, LTPBP2- Related Weill-Marchesani Syndrome

, MD and , MDCM.

Author Information
, MD
Medical Officer, Obstetric and Pediatric Pharmacology Branch
Center for Research for Mothers and Children
The Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland
, MDCM
Chair, Department of Ophthalmology
University of Alberta
Royal Alexandra Hospital
Edmonton, Alberta

Initial Posting: ; Last Update: February 14, 2013.

Summary

Disease characteristics. Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterized by abnormalities of the lens of the eye, proportionate short stature, brachydactyly, and joint stiffness. The ocular problems, typically recognized in childhood, include microspherophakia (small spherical lens), myopia secondary to the abnormal shape of the lens, ectopia lentis (abnormal position of the lens), and glaucoma, which can lead to blindness. Height of adult males is 142-169 cm; height of adult females is 130-157 cm. Autosomal recessive and autosomal dominant WMS cannot be distinguished by clinical findings alone.

Diagnosis/testing. Diagnosis relies on clinical findings; molecular genetic testing can help confirm the diagnosis. Mutations in ADAMTS10 are known to cause autosomal recessive WMS. Recently a mutation in LTPBP2 has been reported one family with autosomal recessive inheritance. A mutation in FBN1 has been identified in one family with autosomal dominant WMS.

Management. Treatment of manifestations: Early detection and removal of an ectopic lens to decrease the possibility of pupillary block and glaucoma. Surgical management of glaucoma can include peripheral iridectomy to prevent or relieve pupillary block and trabeculectomy in advanced chronic angle closure glaucoma; medical treatment of glaucoma is difficult because of paradoxical response to miotics and mydriatics.

Prevention of secondary complications: Airway management during anesthesia can be difficult because of stiff joints, poorly aligned teeth, and maxillary hypoplasia.

Surveillance: Periodic ophthalmic examinations for early detection and removal of an ectopic lens.

Agents/circumstances to avoid: Ophthalmic miotics and mydriatics because they can induce pupillary block.

Genetic counseling. FBN1-related WMS is inherited in an autosomal dominant manner. Most individuals diagnosed with autosomal dominant WMS have an affected parent. The proportion of cases caused by de novo mutations is unknown. Each child of an individual with autosomal dominant WMS has a 50% chance of inheriting the mutation. ADAMTS10-related WMS and LTBP2-related WMS are inherited in an autosomal recessive manner. The parents of a child with autosomal recessive WMS are obligate heterozygotes and therefore carry one mutant allele. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis is possible for pregnancies at increased risk for WMS if the disease-causing mutation(s) in the family are known.

Diagnosis

Clinical Diagnosis

Diagnostic criteria for Weill-Marchesani syndrome (WMS) have not been formally established. The clinical diagnosis of WMS is considered when the following are observed:

  • Eye anomalies including microspherophakia and ectopia lentis
  • Short stature
  • Brachydactyly
  • Joint stiffness
  • Heart defects (occasional)

A WMS-like syndrome has been described in individuals who manifest the above features with the exception of brachydactyly and joint stiffness. [Morales et al 2009].

Molecular Genetic Testing

Genes

Clinical testing

Table 1. Summary of Molecular Genetic Testing Used in Weill-Marchesani Syndrome

Gene SymbolProportion of Weill-Marchesani Syndrome Attributed to Mutations in This GeneTest MethodMutations Detected
ADAMTS10Mutations identified in the vast majority of patientsSequence analysisSequence variants 1, 2
Deletion / duplication analysis 3Unknown; none reported 4, 5
FBN1Mutation identified in one familySequence analysisSequence variants 1
Deletion / duplication analysis 3In-frame exonic / multiexonic deletions 5
LTBP2Mutation identified in one familySequence analysisSequence variants 1

1. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected.

2. Analysis of the entire coding region identified homozygous mutations in two large consanguineous families and one simplex case (i.e., a single occurrence in a family) [Dagoneau et al 2004].

3. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

4. No deletions or duplications involving ADAMTS10 have been reported to cause ADAMTS10-related Weill-Marchesani syndrome.

5. De Backer et al [2007]

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Information on specific allelic variants may be available in Molecular Genetics (see Table A. Genes and Databases and/or Pathologic allelic variants).

Testing Strategy

To confirm/establish the diagnosis in a proband. The diagnosis is primarily established by clinical findings, but molecular genetic testing can help to confirm the diagnosis.

Carrier testing for relatives at risk for autosomal recessive WMS requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for autosomal recessive WMS and are not at risk of developing the disorder.

Prenatal diagnosis for pregnancies at risk for autosomal recessive WMS requires prior identification of the disease-causing mutations in the family.

Clinical Description

Natural History

Weill-Marchesani syndrome (WMS) is a connective tissue disorder that usually presents in childhood with short stature and/or ocular problems. The autosomal recessive and autosomal dominant forms of WMS share clinical manifestations in the following systems [Faivre et al 2003a].

Eyes. The mean age of recognition of an ocular problem is 7.5 years. Microspherophakia (small spherical lens) is the most important manifestation of WMS. Microspherophakia results in lenticular myopia (i.e., myopia primarily resulting from abnormal shape of the lens), ectopia lentis (abnormal position of the lens), and glaucoma (elevation of the intraocular pressure).

  • Lenticular myopia is usually the first ophthalmologic finding.
  • Ectopia lentis usually results in downward displacement of the lens.
  • Glaucoma is the most serious complication because it can lead to blindness. In most cases glaucoma results from pupillary block resulting from forward movement of the lens or by dislocation of the lens into the anterior chamber. Increased central corneal thickness has been recognized as a pathologic feature of WMS that may lead to overestimation of intraocular pressure by applanation tonometers [Razeghinejad & Safavian 2006].

Loss of vision occurs earlier in WMS and is more severe than in other lens dislocation syndromes. In some cases, lens dislocation and pupillary block appear after blunt trauma to the eye weakens the zonular fibers.

Presenile vitreous liquefaction has been described in a large family with autosomal dominant WMS [Evereklioglu et al 1999].

Retinal vascular tortuosity in the absence of congenital heart disease has been described in one affected individual [Gallagher et al 2011].

Retinitis pigmentosa has been reported in an affected female age 14 years [Jethani et al 2007].

Growth. Proportionate short stature is an essential part of the syndrome. An adult male with WMS is expected to achieve a height of 142-169 cm while an adult female is expected to achieve a height of 130-157 cm.

Digits and joints. Digits are short (brachydactyly) and joints are stiff.

Heart abnormalities are occasionally seen and include patent ductus arteriosus and pulmonary stenosis.

Mentation is usually normal.

Genotype-Phenotype Correlations

Genotype-phenotype correlations are limited. Faivre et al [2003a] reviewed 128 cases from the literature (57 autosomal recessive, 50 autosomal dominant, and 21 simplex [i.e., a single occurrence in a family]) and concluded that the three groups showed no significant differences in myopia, glaucoma, cataract, short stature, brachydactyly, thick skin, muscular build, or intellectual disability. Findings for which differences were found are shown in Table 2.

Table 2. Phenotypic Differences in Weill-Marchesani Syndrome by Mode of Inheritance

FindingPresent in Individuals with:
Autosomal Recessive WMSAutosomal Dominant WMS
Microspherophakia94%74%
Ectopia lentis64%84%
Joint limitations49%77%
Cardiac anomalies39%13%

Faivre et al [2003a] were unable to distinguish individuals with autosomal recessive WMS from those with autosomal dominant WMS by clinical findings alone.

Penetrance

The penetrance in those with autosomal recessive WMS caused by homozygous ADAMTS10 mutations is thought to be 100%.

The penetrance for autosomal dominant WMS is incomplete and the phenotype shows variable expressivity. The expressivity for autosomal dominant WMS is 91.7% for short stature, 71.4% for brachydactyly, and 45.2% for abnormal gonioscopic findings, as outlined by Kloepfer & Rosenthal [1955].

Nomenclature

Other terms previously used to refer to Weill-Marchesani syndrome:

  • Spherophakia-brachymorphia syndrome
  • Mesodermal dysmorphodystrophy, congenital

Prevalence

WMS is described as being very rare. Prevalence has been estimated at 1:100,000 population.

Differential Diagnosis

Ectopia lentis can also occur in the following conditions [Fuchs & Rosenberg 1998]. All, however, are clinically distinct from Weill-Marchesani syndrome (WMS):

  • Marfan syndrome is a disorder of connective tissue with a high degree of clinical variability. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. Myopia and ectopia lentis are the most common ocular features. Skeletal system involvement is characterized by bone overgrowth and joint laxity. The extremities are disproportionately long for trunk size (dolichostenomelia). Overgrowth of the ribs can result in pectus excavatum or pectus carinatum. Scoliosis is common and can be mild or severe and progressive. Cardiovascular manifestations include dilatation of the aorta at the level of the sinuses of Valsalva, a predisposition for aortic tear and rupture, mitral valve prolapse with or without regurgitation, tricuspid valve prolapse, and enlargement of the proximal pulmonary artery. FBN1 is the only gene known to be associated with Marfan syndrome and therefore Marfan syndrome is allelic to autosomal dominant WMS. Inheritance is autosomal dominant.
  • Homocystinuria is a metabolic disorder caused by cystathionine β-synthase deficiency; it is characterized by developmental delay/intellectual disability, ectopia lentis (usually inferior), severe myopia, skeletal abnormalities, and thromboembolism. Individuals are often tall and slender with an asthenic habitus ("marfanoid"). Other features that may occur include seizures, psychiatric problems, and extrapyramidal signs including dystonia, hypopigmentation, pancreatitis, malar flush, and livedo reticularis. The cardinal biochemical features of homocystinuria are markedly increased concentrations of plasma homocystine, total homocysteine, and methionine; increased concentration of urine homocystine; and reduced cystathionineβ-synthase (CBS) enzyme activity. CBS is the only gene known to be associated with homocystinuria caused by cystathionine β-synthase deficiency. Inheritance is autosomal recessive.
  • Sulfite oxidase deficiency is a rare disorder of lens luxation with severe neurologic symptoms: untreatable seizures, opisthotonus, attenuated growth of the brain, and intellectual disability. It results from an isolated deficiency in the enzyme sulfite oxidase, which is responsible for the oxidation of sulfite to sulfate or as molybdenum cofactor deficiency. Inheritance is autosomal recessive.
  • Hyperlysinemia is a rare metabolic disorder found to be caused by mutation in the gene encoding alpha-aminoadipic semialdehyde synthase. Inheritance is autosomal recessive.
  • Simple dominant ectopia lentis. Mutations in FBN1 have been identified in some families. Inheritance is autosomal dominant.
  • Ectopia lentis and pupilae. In this condition the lens and the pupil are usually displaced in opposite directions. Inheritance is autosomal recessive.
  • Glaucoma-lens ectopia-microspherophakia-stiffness-shortness (GEMSS) syndrome has features resembling WMS. Inheritance is autosomal dominant [Verloes et al 1992].
  • Mutations in ADAMTS17 have been described in one family with WMS-like symptoms [Morales et al 2009].

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with Weill-Marchesani syndrome (WMS), the following evaluations should be performed:

  • Complete ophthalmologic examination
  • Evaluation by a medical geneticist
  • Cardiac echocardiogram

Treatment of Manifestations

It is not possible to generalize the management of the ocular complications of WMS.

  • The medical treatment of glaucoma is difficult because of paradoxical response to miotics and mydriatics.
  • A peripheral iridectomy should be performed to prevent or relieve pupillary block [Chang et al 2002, Ritch et al 2003].
  • Lens extraction and/or trabeculectomy may be necessary in some persons with advanced chronic angle closure glaucoma [Harasymowycz & Wilson 2004].
  • Individuals with WMS were recently reported to have increased central corneal thickness, which needs to be considered in the diagnosis and follow-up of glaucoma because increased central corneal thickness may lead to overestimation of intraocular pressure by applanation tonometers [Razeghinejad & Safavian 2006].

Prevention of Secondary Complications

Airway management during anesthesia can be difficult in persons with WMS because of stiff joints, poorly aligned teeth, and maxillary hypoplasia [Dal et al 2003, Karabiyik 2003, Riad et al 2006].

Surveillance

Periodic ophthalmic examinations for early detection and removal of an ectopic lens can help decrease the possibility of pupillary block and glaucoma.

Agents/Circumstances to Avoid

Use of ophthalmic miotics and mydriatics should be avoided as they can induce pupillary block.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

The protein product of ADAMTS10 could be a potential therapeutic target for the treatment of autosomal recessive WMS [Jones 2006].

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

ADAMTS10- and LTPBP2-related Weill-Marchesani syndrome are inherited in an autosomal recessive manner.

FBN1-related Weill-Marchesani syndrome is inherited in an autosomal dominant manner.

Faivre et al [2003a] reviewed 128 cases from the literature and determined that 57 (45%) were autosomal recessive; 50 (39%) were autosomal dominant; and 21 (16%) were simplex (i.e., a single occurrence in a family) in whom the mode of inheritance could not be determined on clinical findings alone.

Risk to Family Members — Autosomal Dominant Inheritance

Parents of a proband

  • Most individuals diagnosed with autosomal dominant WMS have an affected parent.
  • A proband with autosomal dominant WMS may have the disorder as the result of a new gene mutation. The proportion of cases caused by de novo mutations is unknown.
  • Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include ophthalmologic examination for detection of possible microspherophakia and detailed examination by a medical geneticist. Evaluation of parents may determine that one is affected but has escaped previous diagnosis because of a milder phenotypic presentation. Therefore, an apparently negative family history cannot be confirmed until appropriate evaluations have been performed.

Note: (1) Although most individuals diagnosed with autosomal dominant WMS have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. (2) If the parent is the individual in whom the mutation first occurred s/he may have somatic mosaicism for the mutation and may be mildly/minimally affected.

Sibs of a proband

  • The risk to the sibs of the proband depends on the genetic status of the proband's parents.
  • If a parent of the proband is affected, the risk to the sibs is 50%.
  • When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low.

Offspring of a proband. Each child of an individual with autosomal dominant WMS has a 50% chance of inheriting the mutation.

Other family members of a proband. The risk to other family members depends on the status of the proband's parents. If a parent is affected, his or her family members may be at risk.

Risk to Family Members — Autosomal Recessive Inheritance

Parents of a proband

  • The parents of an affected individual are obligate heterozygotes and therefore carry one mutant allele.
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. The offspring of an individual with autosomal recessive WMS are obligate heterozygotes (carriers) for a disease-causing mutation.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing of at-risk relatives is possible if the mutations have been identified in the family.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the disease-causing mutation(s) have been identified in the family, prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at ~15-18 weeks’ gestation) or chorionic villus sampling (usually performed at ~10-12 weeks’ gestation).

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutation(s) have been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Children's Glaucoma Foundation
    2 Longfellow Place
    Suite 201
    Boston MA 02114
    Phone: 617-227-3011
    Fax: 617-227-9538
    Email: info@childrensglaucoma.com
  • CongenitalHeartDefects.com
  • Human Growth Foundation (HGF)
    997 Glen Cove Avenue
    Suite 5
    Glen Head NY 11545
    Phone: 800-451-6434 (toll-free)
    Fax: 516-671-4055
    Email: hgf1@hgfound.org
  • MAGIC Foundation
    6645 West North Avenue
    Oak Park IL 60302
    Phone: 800-362-4423 (Toll-free Parent Help Line); 708-383-0808
    Fax: 708-383-0899
    Email: info@magicfoundation.org
  • National Eye Institute
    31 Center Drive
    MSC 2510
    Bethesda MD 20892-2510
    Phone: 301-496-5248
    Email: 2020@nei.nih.gov

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. Weill-Marchesani Syndrome: Genes and Databases

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Weill-Marchesani Syndrome (View All in OMIM)

134797FIBRILLIN 1; FBN1
277600WEILL-MARCHESANI SYNDROME 1; WMS1
602091LATENT TRANSFORMING GROWTH FACTOR-BETA-BINDING PROTEIN 2; LTBP2
608328WEILL-MARCHESANI SYNDROME 2; WMS2
608990A DISINTEGRIN-LIKE AND METALLOPROTEINASE WITH THROMBOSPONDIN TYPE 1 MOTIF, 10; ADAMTS10
614819WEILL-MARCHESANI SYNDROME 3; WMS3

Molecular Genetic Pathogenesis

Weill-Marchesani syndrome (WMS) is a disorder of the connective tissue caused by mutations in ADAMTS10. The protein product of ADAMTS10 belongs to the ADAMTS family of proteins, believed to be anchored to the extracellular matrix. The disorder may also be caused by mutations in FBN1 and recently a direct interaction between the protein products encoded by ADAMTS10 and FBN1 has been demonstrated; the ADAMTS10 protein promotes FBN1 deposition in extracellular matrix of cultured fibroblasts [Kutz et al 2011].

ADAMTS10

Normal allelic variants. ADAMTS10 contains 24 coding exons.

Pathologic allelic variants. Dagoneau et al [2004] reported three distinct nonsense and frameshift mutations in ADAMTS10 in three families with the autosomal recessive form of WMS.

Normal gene product. ADAMTS10 encodes a protein that belongs to a family of metalloproteases, ADAMTS (a disintegrin-like and metalloprotease with thrombospondin motifs). ADAMTS-10 differs from other members of the ADAMTS family by the presence of its five TS domains and a unique C-terminal PLAC (protease and lacunin) domain and is closely related to ADAMTS6. Studies of the normal expression of ADAMTS10 showed that it is expressed in skin, fetal chondrocytes, and fetal and adult heart [Dagoneau et al 2004].

Abnormal gene product. Unknown

FBN1

Normal allelic variants. FBN1 is a large gene comprising 65 exons.

Pathologic allelic variants. Heterozygosity for a 24-bp deletion in FBN1 has been identified by Faivre et al [2003b] in one family with autosomal dominant Weill-Marchesani syndrome.

Normal gene product. FBN1 encodes a member of the fibrillin family. The encoded protein is a large, 350-kd extracellular matrix glycoprotein that serves as a structural component of 10- to 12-nm calcium-binding microfibrils. These microfibrils provide force bearing structural support in elastic and non-elastic connective tissue throughout the body.

Abnormal gene product. Unknown

LTBP2

Normal allelic variants. LTBP2 comprises 35 exons.

Pathologic allelic variants. Haji-Seyed-Javadi et al [2012] identified homozygosity for a missense mutation in LTBP2 in a large consanguineous family with Well Marchesani syndrome.

Normal gene product. The protein encoded by LTBP2 belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP), which are extracellular matrix proteins with multi-domain structure.

The 1,821-amino acid protein consists of 20 epidermal growth factor (EGF)-like domains, four transforming growth factor-beta binding protein (TB)-like modules (each containing eight cysteine residues), and an N-terminal signal peptide.

Abnormal gene product. Unknown

References

Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page Image PubMed.jpg

Literature Cited

  1. Ben Yahia S, Ouechtati F, Jelliti B, Nouira S, Chakroun S, Abdelhak S, Khairallah M. Clinical and genetic investigation of isolated microspherophakia in a consanguineous Tunisian family. J Hum Genet. 2009;54:550–3. [PubMed: 19696795]
  2. Chang BM, Liebmann JM, Ritch R. Angle closure in younger patients. Trans Am Ophthalmol Soc. 2002;100:201–12. [PMC free article: PMC1358963] [PubMed: 12545694]
  3. Dagoneau N, Benoist-Lasselin C, Huber C, Faivre L, Megarbane A, Alswaid A, Dollfus H, Alembik Y, Munnich A, Legeai-Mallet L, Cormier-Daire V. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet. 2004;75:801–6. [PMC free article: PMC1182109] [PubMed: 15368195]
  4. Dal D, Sahin A, Aypar U. Anesthetic management of a patient with Weill-Marchesani syndrome. Acta Anaesthesiol Scand. 2003;47:369–70. [PubMed: 12648208]
  5. De Backer J, Loeys B, Leroy B, Coucke P, Dietz H, De Paepe A. Utility of molecular analyses in the exploration of extreme intrafamilial variability in the Marfan syndrome. Clin Genet. 2007;72:188–98. [PubMed: 17718856]
  6. Desir J, Sznajer Y, Depasse F, Roulez F, Schrooyen M, Meire F, Abramowicz M. LTBP2 null mutations in an autosomal recessive ocular syndrome with megalocornea, spherophakia, and secondary glaucoma. Europ. J. Hum. Genet. 2010;18:761–7. [PMC free article: PMC2987369] [PubMed: 20179738]
  7. Evereklioglu C, Hepsen IF, Er H. Weill-Marchesani syndrome in three generations. Eye. 1999;13:773–7. [PubMed: 10707143]
  8. Faivre L, Dollfus H, Lyonnet S, Alembik Y, Mégarbané A, Samples J, Gorlin RJ, Alswaid A, Feingold J, Le Merrer M, Munnich A, Cormier-Daire V. Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet A. 2003a;123A:204–7. [PubMed: 14598350]
  9. Faivre L, Gorlin RJ, Wirtz MK, Godfrey M, Dagoneau N, Samples JR, Le Merrer M, Collod-Beroud G, Boileau C, Munnich A, Cormier-Daire V. In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome. J Med Genet. 2003b;40:34–6. [PMC free article: PMC1735272] [PubMed: 12525539]
  10. Faivre L, Megarbane A, Alswaid A, Zylberberg L, Aldohayan N, Campos-Xavier B, Bacq D, Legeai-Mallet L, Bonaventure J, Munnich A, Cormier-Daire V. Homozygosity mapping of a Weill-Marchesani syndrome locus to chromosome 19p13.3-p13.2. Hum Genet. 2002;110:366–70. [PubMed: 11941487]
  11. Fuchs J, Rosenberg T. Congenital ectopia lentis. A Danish national survey. Acta Ophthalmol Scand. 1998;76:20–6. [PubMed: 9541430]
  12. Gallagher K, Salam T, Sin B, Gupta S, Zambarakji H. Retinal vascular tortuosity in a patient with Weill-Marchesani syndrome. Case Rep Ophthalmol Med. 2011;2011:952543. [PMC free article: PMC3350144] [PubMed: 22606482]
  13. Haji-Seyed-Javadi R, Jelodari-Mamaghani S, Paylakhi SH, Yazdani S, Nilforushan N, Fan JB, Klotzle B, Mahmoudi MJ, Ebrahimian MJ, Chelich N, Taghiabadi E, Kamyab K, Boileau C, Paisan-Ruiz C, Ronaghi M, Elahi E. LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix. Hum Mutat. 2012;33:1182–7. [PubMed: 22539340]
  14. Harasymowycz P, Wilson R. Surgical treatment of advanced chronic angle closure glaucoma in Weill-Marchesani syndrome. J Pediatr Ophthalmol Strabismus. 2004;41:295–9. [PubMed: 15478742]
  15. Jethani J, Mishra A, Shetty S, Vijayalakshmi P. Weill-Marchesani syndrome associated with retinitis pigmentosa. Indian J Ophthalmol. 2007;55:142–3. [PubMed: 17322607]
  16. Jones GC. ADAMTS proteinases: potential therapeutic targets? Curr Pharm Biotechnol. 2006;7:25–31. [PubMed: 16472131]
  17. Karabiyik L. Airway management of a patient with Weill-Marchesani syndrome. J Clin Anesth. 2003;15:214–6. [PubMed: 12770659]
  18. Khan AO, Aldahmesh MA, Alkuraya FS. Congenital megalocornea with zonular weakness and childhood lens-related secondary glaucoma--a distinct phenotype caused by recessive LTBP2 mutations. Molec. Vis. 2011;17:2570–9. [PMC free article: PMC3198484] [PubMed: 22025892]
  19. Kloepfer HW, Rosenthal JW. Possible genetic carriers in the spherophakia-brachymorphia syndrome. Am J Hum Genet. 1955;7:398–425. [PMC free article: PMC1716673] [PubMed: 13275462]
  20. Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH. A homozygous mutation in LTBP2 causes isolated microspherophakia. Hum Genet. 2010;128:365–71. [PubMed: 20617341]
  21. Kutz WE, Wang LW, Bader HL, Majors AK, Iwata K, Traboulsi EI, Sakai LY, Keene DR, Apte SS. ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in extracellular matrix of cultured fibroblasts. J Biol Chem. 2011;286:17156–67. [PMC free article: PMC3089559] [PubMed: 21402694]
  22. Le Goff C, Mahaut C, Wang LW, Allali S, Abhyankar A, Jensen S, Zylberberg L, Collod-Beroud G, Bonnet D, Alanay Y, Brady AF, Cordier MP, Devriendt K, Genevieve D, Kiper PÖ, Kitoh H, Krakow D, Lynch SA, Le Merrer M, Mégarbane A, Mortier G, Odent S, Polak M, Rohrbach M, Sillence D, Stolte-Dijkstra I, Superti-Furga A, Rimoin DL, Topouchian V, Unger S, Zabel B, Bole-Feysot C, Nitschke P, Handford P, Casanova JL, Boileau C, Apte SS, Munnich A, Cormier-Daire V. Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet. 2011;89:7–14. [PMC free article: PMC3135800] [PubMed: 21683322]
  23. Megarbane A, Mustapha M, Bleik J, Waked N, Delague V, Loiselet J. Exclusion of chromosome 15q21.1 in autosomal-recessive Weill-Marchesani syndrome in an inbred Lebanese family. Clin Genet. 2000;58:473–8. [PubMed: 11149617]
  24. Morales J, Al-Sharif L, Khalil DS, Shinwari JM, Bavi P, Al-Mahrouqi RA, Al-Rajhi A, Alkuraya FS, Meyer BF, Al Tassan N. Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature. Am J Hum Genet. 2009;85:558–68. [PMC free article: PMC2775842] [PubMed: 19836009]
  25. Razeghinejad MR, Safavian H. Central corneal thickness in patients with Weill-Marchesani syndrome. Am J Ophthalmol. 2006;142:507–8. [PubMed: 16935606]
  26. Riad W, Abouammoh M, Fathy M. Anesthetic characteristics and airway evaluation of patients with Weill-Marchesani syndrome. Middle East J Anesthesiol. 2006;18:725–31. [PubMed: 16749567]
  27. Ritch R, Chang BM, Liebmann JM. Angle closure in younger patients. Ophthalmology. 2003;110:1880–9. [PubMed: 14522758]
  28. Verloes A, Hermia JP, Galand A, Koulischer L, Dodinval P. Glaucoma-lens ectopia-microspherophakia-stiffness-shortness (GEMSS) syndrome: a dominant disease with manifestations of Weill-Marchesani syndromes. Am J Med Genet. 1992;44:48–51. [PubMed: 1519650]

Suggested Reading

  1. Burakgazi AZ, Ozbek Z, Rapuano CJ, Rhee DJ. Long-term complications of iris-claw phakic intraocular lens implantation in Weill-Marchesani syndrome. Cornea. 2006;25:361–3. [PubMed: 16633042]
  2. Chu BS. Weill-Marchesani syndrome and secondary glaucoma associated with ectopia lentis. Clin Exp Optom. 2006;89:95–9. [PubMed: 16494613]
  3. Collod-Beroud G, Le Bourdelles S, Ades L, Ala-Kokko L, Booms P, Boxer M, Child A, Comeglio P, De Paepe A, Hyland JC, Holman K, Kaitila I, Loeys B, Matyas G, Nuytinck L, Peltonen L, Rantamaki T, Robinson P, Steinmann B, Junien C, Beroud C, Boileau C. Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database. Hum Mutat. 2003;22:199–208. [PubMed: 12938084]
  4. Madugula A, Chandrasekaran R, Rakesh G. Homatropine and psychosis in Weill-Marchesani syndrome. J Am Acad Child Adolesc Psychiatry. 2006;45:769–70. [PubMed: 16832313]
  5. Saricaoglu MS, Sengun A, Karakurt A, Colluoglu Z. Autosomal dominant Weill-Marchesani syndrome and glaucoma management. Saudi Med J. 2005;26:1468–9. [PubMed: 16155673]
  6. Wentzloff JN, Kaldawy RM, Chen TC. Weill-Marchesani syndrome. J Pediatr Ophthalmol Strabismus. 2006;43:192. [PubMed: 16761646]

Chapter Notes

Revision History

  • 14 February 2013 (me) Comprehensive update posted live
  • 1 November 2007 (me) Review posted to live Web site
  • 3 August 2007 (et) Original submission
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