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Weill-Marchesani syndrome 1(WMS1)

MedGen UID:
358270
Concept ID:
C1869114
Disease or Syndrome
Synonyms: ADAMTS10-Related Weill-Marchesani Syndrome; MESODERMAL DYSMORPHODYSTROPHY, CONGENITAL; SPHEROPHAKIA-BRACHYMORPHIA SYNDROME; Weill-Marchesani Syndrome, Autosomal Recessive; WMS1
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): ADAMTS10 (19p13.2)
OMIM®: 277600

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, 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. [from GeneReviews]
Authors:
Ekaterini Tsilou  |  Ian M MacDonald   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). Genetic Heterogeneity of Weill-Marchesani Syndrome A phenotypically similar, autosomal dominant form of WMS (WMS2; 608328) is caused by mutation in the FBN1 gene on chromosome 15q21. Autosomal recessive WMS3 (614819) is caused by mutation in the LTBP2 gene (602091) on chromosome 14q24. A WMS-like syndrome (613195), in which affected individuals exhibit key features of WMS but do not display brachydactyly or decreased joint flexibility, is caused by mutation in the ADAMTS17 gene (607511) on chromosome 15q24.  http://www.omim.org/entry/277600
From GHR
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.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.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.Occasionally, heart defects or an abnormal heart rhythm can occur in people with Weill-Marchesani syndrome.  https://ghr.nlm.nih.gov/condition/weill-marchesani-syndrome

Clinical features

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 is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term "early-onset glaucoma" may be used when the disorder appears before the age of 40.In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Acquired Abnormality
A cataract is a clouding of the lens in your eye. It affects your vision. Cataracts are very common in older people. By age 80, more than half of all Americans either have a cataract or have had cataract surgery. A cataract can occur in either or both eyes. It cannot spread from one eye to the other. Common symptoms are. -Blurry vision. -Colors that seem faded. -Glare - headlights, lamps or sunlight may seem too bright. You may also see a halo around lights. -Not being able to see well at night. -Double vision . -Frequent prescription changes in your eye wear . Cataracts usually develop slowly. New glasses, brighter lighting, anti-glare sunglasses or magnifying lenses can help at first. Surgery is also an option. It involves removing the cloudy lens and replacing it with an artificial lens. Wearing sunglasses and a hat with a brim to block ultraviolet sunlight may help to delay cataracts. NIH: National Eye Institute.
Severe 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.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Finding
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used to describe a series of Mendelian diseases characterized by distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here, however, it is preferable to described the observed phenotypic abnormalities precisely.
Broad palm
MedGen UID:
75535
Concept ID:
C0264142
Disease or Syndrome
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.
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.
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
Disease or Syndrome
constriction in the opening of the aortic valve or of the supravalvular or subvalvular regions.
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.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Anatomical Abnormality
Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Finding
backflow of blood from the left ventricle into the left atrium, owing to imperfect functioning of the mitral valve.
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) or just below the pulmonary valve (infundibular stenosis).
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.
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.
Scoliosis
MedGen UID:
21278
Concept ID:
C0037932
Finding
The presence of an abnormal lateral curvature of the spine.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
A feeling of tension or tightness in one or more joints.
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.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used to describe a series of Mendelian diseases characterized by distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here, however, it is preferable to described the observed phenotypic abnormalities precisely.
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.
Broad skull
MedGen UID:
98413
Concept ID:
C0424693
Finding
Increased width of the skull.
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 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.
Broad ribs
MedGen UID:
336390
Concept ID:
C1848654
Finding
Increased width of ribs
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.
Broad phalanges of the hand
MedGen UID:
867033
Concept ID:
C4021391
Anatomical Abnormality
Increased width of the phalanges of the hand.
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.
Abnormality of the teeth
MedGen UID:
78084
Concept ID:
C0262444
Finding
Any abnormality of the teeth.
Broad skull
MedGen UID:
98413
Concept ID:
C0424693
Finding
Increased width of the skull.
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.
Misalignment of teeth
MedGen UID:
377692
Concept ID:
C1852504
Finding
Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.
Shallow orbits
MedGen UID:
351328
Concept ID:
C1865244
Finding
Reduced depth of the orbits associated with prominent-appearing ocular globes.

Recent clinical studies

Diagnosis

Steinkellner H, Etzler J, Gogoll L, Neesen J, Stifter E, Brandau O, Laccone F
Eur J Hum Genet 2015 Sep;23(9):1186-91. Epub 2014 Dec 3 doi: 10.1038/ejhg.2014.264. PMID: 25469541Free PMC Article

Prognosis

Steinkellner H, Etzler J, Gogoll L, Neesen J, Stifter E, Brandau O, Laccone F
Eur J Hum Genet 2015 Sep;23(9):1186-91. Epub 2014 Dec 3 doi: 10.1038/ejhg.2014.264. PMID: 25469541Free PMC Article

Clinical prediction guides

Steinkellner H, Etzler J, Gogoll L, Neesen J, Stifter E, Brandau O, Laccone F
Eur J Hum Genet 2015 Sep;23(9):1186-91. Epub 2014 Dec 3 doi: 10.1038/ejhg.2014.264. PMID: 25469541Free PMC Article

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