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Weill-Marchesani syndrome 2, dominant(WMS2; GEMSS)

MedGen UID:
358388
Concept ID:
C1869115
Disease or Syndrome
Synonyms: FBN1-Related Weill-Marchesani Syndrome; Glaucoma, Ectopia, Microspherophakia, Stiff joints and Short stature syndrome; Weill-Marchesani syndrome 2; Weill-Marchesani Syndrome, Autosomal Dominant
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FBN1 (15q21.1)
 
Monarch Initiative: MONDO:0012013
OMIM®: 608328
Orphanet: ORPHA2084

Disease characteristics

Excerpted from the GeneReview: Weill-Marchesani Syndrome
Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterized by abnormalities of the lens of the eye, short stature, brachydactyly, joint stiffness, and cardiovascular defects. 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 WMS cannot be distinguished from autosomal dominant WMS by clinical findings alone. [from GeneReviews]
Authors:
Pauline Marzin  |  Valérie Cormier-Daire  |  Ekaterini Tsilou   view full author information

Additional descriptions

From OMIM
Weill-Marchesani syndrome is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and lens abnormalities (Faivre et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of WMS, see 277600.  http://www.omim.org/entry/608328
From MedlinePlus Genetics
Occasionally, heart defects or an abnormal heart rhythm can occur in people with Weill-Marchesani syndrome.

An eye abnormality called microspherophakia is characteristic of Weill-Marchesani syndrome. This term 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). Many people with Weill-Marchesani syndrome develop glaucoma, an eye disease that increases the pressure in the eye and can lead to blindness.

The major signs and symptoms of Weill-Marchesani syndrome include short stature, eye abnormalities, unusually short fingers and toes (brachydactyly), and joint stiffness. Adult height for men with Weill-Marchesani syndrome ranges from 4 feet, 8 inches to 5 feet, 6 inches. Adult height for women with this condition ranges from 4 feet, 3 inches to 5 feet, 2 inches.

Weill-Marchesani syndrome is a disorder of connective tissue. Connective tissue forms the body's supportive framework, providing structure and strength to the muscles, joints, organs, and skin.  https://medlineplus.gov/genetics/condition/weill-marchesani-syndrome

Clinical features

From HPO
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Broad palm
MedGen UID:
75535
Concept ID:
C0264142
Congenital Abnormality
For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length.
Flexion contracture of toe
MedGen UID:
237248
Concept ID:
C1406835
Finding
One or more bent (flexed) toe joints that cannot be straightened actively or passively.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Broad metacarpals
MedGen UID:
330796
Concept ID:
C1842229
Finding
Abnormally broad metacarpal bones.
Broad metatarsal
MedGen UID:
330797
Concept ID:
C1842231
Finding
Increased side-to-side width of a metatarsal bone.
Short finger
MedGen UID:
334977
Concept ID:
C1844548
Anatomical Abnormality
Abnormally short finger associated with developmental hypoplasia.
Broad phalanges of the hand
MedGen UID:
867033
Concept ID:
C4021391
Anatomical Abnormality
Increased width of the phalanges of the hand.
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Ascending aortic dissection
MedGen UID:
322966
Concept ID:
C1836653
Disease or Syndrome
A separation of the layers within the wall of the ascending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Proportionate short stature
MedGen UID:
163901
Concept ID:
C0878660
Finding
A kind of short stature in which different regions of the body are shortened to a comparable extent.
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
Thickened helices
MedGen UID:
325240
Concept ID:
C1837732
Finding
Increased thickness of the helix of the ear.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Broad skull
MedGen UID:
98413
Concept ID:
C0424693
Finding
Increased width of the skull.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Thin bony cortex
MedGen UID:
318844
Concept ID:
C1833325
Finding
Abnormal thinning of the cortical region of bones.
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Increased width of ribs
Short metatarsal
MedGen UID:
341358
Concept ID:
C1849020
Finding
Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.
Spinal canal stenosis
MedGen UID:
396107
Concept ID:
C1861329
Anatomical Abnormality
An abnormal narrowing of the spinal canal.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Narrow palate
MedGen UID:
278045
Concept ID:
C1398312
Finding
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Tooth malposition
MedGen UID:
377692
Concept ID:
C1852504
Finding
Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.
Depressed glabella
MedGen UID:
869037
Concept ID:
C4023455
Anatomical Abnormality
Posterior positioning of the glabella, i.e., of the midline forehead between the supraorbital ridges.
Striae distensae
MedGen UID:
57541
Concept ID:
C0152459
Acquired Abnormality
Thinned, erythematous, depressed bands of atrophic skin. Initially, striae appear as flattened and thinned, pinkish linear regions of the skin. Striae tend to enlarge in length and become reddish or purplish. Later, striae tend to appear as white, depressed bands that are parallel to the lines of skin tension. Striae distensae occur most often in areas that have been subject to distension such as the lower back, buttocks, thighs, breast, abdomen, and shoulders.
Thickened skin
MedGen UID:
66024
Concept ID:
C0241165
Finding
Laminar thickening of skin.
Lack of skin elasticity
MedGen UID:
892876
Concept ID:
C4021998
Finding
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Ectopia lentis
MedGen UID:
41704
Concept ID:
C0013581
Congenital Abnormality
Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Lens luxation
MedGen UID:
6043
Concept ID:
C0023309
Injury or Poisoning
Complete dislocation of the lens of the eye.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Shallow anterior chamber
MedGen UID:
602215
Concept ID:
C0423276
Finding
Reduced depth of the anterior chamber, i.e., the anteroposterior distance between the cornea and the iris is decreased.
Iridodonesis
MedGen UID:
451052
Concept ID:
C0423320
Disease or Syndrome
Tremulousness of the iris on movement of the eye, occurring in subluxation of the lens.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as visual perception below 3/60 and/or a visual field of no greater than 10 degrees in radius around central fixation.
Microspherophakia
MedGen UID:
288328
Concept ID:
C1562061
Congenital Abnormality
Microspherophakia (MSP) is a rare disease characterized by smaller and more spherical lenses than normal bilaterally, an increased anteroposterior thickness of the lens, and highly myopic eyes. Lens dislocation or subluxation may occur, leading to defective accommodation (summary by Ben Yahia et al., 2009). Microspherophakia may occur in association with ectopia lentis and glaucoma, Marfan syndrome (MFS; 154700), and Weill-Marchesani syndrome (WMS; 277600).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Marzin P, Rondeau S, Alessandri JL, Dieterich K, le Goff C, Mahaut C, Mercier S, Michot C, Moldovan O, Miolo G, Rossi M, Van-Gils J, Francannet C, Robert MP, Jaïs JP, Huber C, Cormier-Daire V
J Med Genet 2024 Jan 19;61(2):109-116. doi: 10.1136/jmg-2023-109288. PMID: 37734846
De Backer J
Verh K Acad Geneeskd Belg 2009;71(6):335-71. PMID: 20232788

Recent clinical studies

Etiology

Marzin P, Rondeau S, Alessandri JL, Dieterich K, le Goff C, Mahaut C, Mercier S, Michot C, Moldovan O, Miolo G, Rossi M, Van-Gils J, Francannet C, Robert MP, Jaïs JP, Huber C, Cormier-Daire V
J Med Genet 2024 Jan 19;61(2):109-116. doi: 10.1136/jmg-2023-109288. PMID: 37734846
Newell K, Smith W, Ghoshhajra B, Isselbacher E, Lin A, Lindsay ME
Am J Med Genet A 2017 Sep;173(9):2551-2556. Epub 2017 Jul 11 doi: 10.1002/ajmg.a.38353. PMID: 28696036
Le Goff C, Cormier-Daire V
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):145-53. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31337. PMID: 22791552
Le Goff C, Cormier-Daire V
Pediatr Endocrinol Rev 2009 Mar;6(3):418-23. PMID: 19396027
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
Am J Med Genet A 2003 Dec 1;123A(2):204-7. doi: 10.1002/ajmg.a.20289. PMID: 14598350

Diagnosis

Marzin P, Rondeau S, Alessandri JL, Dieterich K, le Goff C, Mahaut C, Mercier S, Michot C, Moldovan O, Miolo G, Rossi M, Van-Gils J, Francannet C, Robert MP, Jaïs JP, Huber C, Cormier-Daire V
J Med Genet 2024 Jan 19;61(2):109-116. doi: 10.1136/jmg-2023-109288. PMID: 37734846
Reyes-Hernández OD, Palacios-Reyes C, Chávez-Ocaña S, Cortés-Malagón EM, Alonso-Themann PG, Ramos-Cano V, Ramírez-Bello J, Sierra-Martínez M
BMC Musculoskelet Disord 2016 Feb 15;17:79. doi: 10.1186/s12891-016-0935-9. PMID: 26875674Free PMC Article
De Backer J
Verh K Acad Geneeskd Belg 2009;71(6):335-71. PMID: 20232788
Le Goff C, Cormier-Daire V
Pediatr Endocrinol Rev 2009 Mar;6(3):418-23. PMID: 19396027
Evereklioglu C, Hepsen IF, Er H
Eye (Lond) 1999 Dec;13 ( Pt 6):773-7. doi: 10.1038/eye.1999.226. PMID: 10707143

Therapy

Saricaoglu MS, Sengun A, Karakurt A, Colluoglu Z
Saudi Med J 2005 Sep;26(9):1468-9. PMID: 16155673

Prognosis

Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH
Hum Genet 2010 Oct;128(4):365-71. Epub 2010 Jul 9 doi: 10.1007/s00439-010-0858-8. PMID: 20617341
Saricaoglu MS, Sengun A, Karakurt A, Colluoglu Z
Saudi Med J 2005 Sep;26(9):1468-9. PMID: 16155673
Van Meir N, De Smet L
Acta Orthop Belg 2003 Oct;69(5):387-95. PMID: 14648946

Clinical prediction guides

Wang LW, Kutz WE, Mead TJ, Beene LC, Singh S, Jenkins MW, Reinhardt DP, Apte SS
Matrix Biol 2019 Apr;77:117-128. Epub 2018 Sep 7 doi: 10.1016/j.matbio.2018.09.004. PMID: 30201140Free PMC Article
Le Goff C, Cormier-Daire V
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):145-53. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31337. PMID: 22791552
Kumar A, Duvvari MR, Prabhakaran VC, Shetty JS, Murthy GJ, Blanton SH
Hum Genet 2010 Oct;128(4):365-71. Epub 2010 Jul 9 doi: 10.1007/s00439-010-0858-8. PMID: 20617341
De Backer J
Verh K Acad Geneeskd Belg 2009;71(6):335-71. PMID: 20232788
Verloes A, Hermia JP, Galand A, Koulischer L, Dodinval P
Am J Med Genet 1992 Sep 1;44(1):48-51. doi: 10.1002/ajmg.1320440112. PMID: 1519650

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