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Stickler syndrome, type 5(STL5)

MedGen UID:
481972
Concept ID:
C3280342
Disease or Syndrome
Synonyms: COL9A2-Related Stickler Syndrome; STL5
 
Gene (location): COL9A2 (1p34.2)
 
Monarch Initiative: MONDO:0013666
OMIM®: 614284

Disease characteristics

Excerpted from the GeneReview: Stickler Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Pierre Robin sequence); and early-onset degenerative joint disease. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity. [from GeneReviews]
Authors:
Geert Mortier   view full author information

Additional description

From MedlinePlus Genetics
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia), which means they have trouble seeing things that are far away. In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.

In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.

A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.

Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.  https://medlineplus.gov/genetics/condition/stickler-syndrome

Clinical features

From HPO
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).
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Isolated Pierre-Robin syndrome
MedGen UID:
19310
Concept ID:
C0031900
Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulties during the neonatal period (summary by Tan et al., 2013).
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short chin
MedGen UID:
784514
Concept ID:
C3697248
Finding
Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin.
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
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.
Vitreoretinopathy
MedGen UID:
87480
Concept ID:
C0344290
Disease or Syndrome
Ocular abnormality characterized by premature degeneration of the vitreous and the retina that may be associated with increased risk of retinal detachment.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Kandeeban S, Kandale K, Periyasamy P, Bhende M, Bhende P, Sinnakaruppan M, Sarangapani S
Indian J Ophthalmol 2022 Jul;70(7):2578-2583. doi: 10.4103/ijo.IJO_1833_21. PMID: 35791160Free PMC Article
Khan AO, AlAbdi L, Patel N, Helaby R, Hashem M, Abdulwahab F, AlBadr FB, Alkuraya FS
Mol Genet Genomic Med 2021 May;9(5):e1628. Epub 2021 May 5 doi: 10.1002/mgg3.1628. PMID: 33951325Free PMC Article
Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI
Genet Med 2003 Jan-Feb;5(1):21-7. doi: 10.1097/00125817-200301000-00004. PMID: 12544472

Recent clinical studies

Etiology

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Genet Med 2003 Jan-Feb;5(1):21-7. doi: 10.1097/00125817-200301000-00004. PMID: 12544472
Snead MP, Yates JR
J Med Genet 1999 May;36(5):353-9. PMID: 10353778Free PMC Article

Diagnosis

Khan AO, AlAbdi L, Patel N, Helaby R, Hashem M, Abdulwahab F, AlBadr FB, Alkuraya FS
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Xerri O, Bernabei F, Philippakis E, Burin-Des-Roziers C, Barale PO, Laplace O, Monin C, Bremond-Gignac D, Guerrier G, Valleix S, Brezin A, Rothschild PR
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Vilaplana F, Muiños SJ, Nadal J, Elizalde J, Mojal S
Arch Soc Esp Oftalmol 2015 Jun;90(6):264-8. Epub 2015 Mar 25 doi: 10.1016/j.oftal.2014.11.001. PMID: 25817961
Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI
Genet Med 2003 Jan-Feb;5(1):21-7. doi: 10.1097/00125817-200301000-00004. PMID: 12544472

Therapy

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Garg S, Piva A, Sanchez RN, Sadun AA
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Prognosis

Jiang Y, Xiao X, Sun W, Wang Y, Li S, Jia X, Wang P, Hejtmancik JF, Zhang Q
J Transl Med 2024 Jan 19;22(1):75. doi: 10.1186/s12967-024-04886-5. PMID: 38243264Free PMC Article
Rossenwasser-Weiss S, Orenstein N, Zahavi A, Goldenberg-Cohen N
Curr Eye Res 2021 Jul;46(7):1051-1055. Epub 2020 Dec 9 doi: 10.1080/02713683.2020.1855661. PMID: 33295219
Wubben TJ, Branham KH, Besirli CG, Bohnsack BL
Ophthalmic Genet 2018 Oct;39(5):615-618. Epub 2018 Aug 21 doi: 10.1080/13816810.2018.1509355. PMID: 30130436
Vilaplana F, Muiños SJ, Nadal J, Elizalde J, Mojal S
Arch Soc Esp Oftalmol 2015 Jun;90(6):264-8. Epub 2015 Mar 25 doi: 10.1016/j.oftal.2014.11.001. PMID: 25817961
Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI
Genet Med 2003 Jan-Feb;5(1):21-7. doi: 10.1097/00125817-200301000-00004. PMID: 12544472

Clinical prediction guides

Jiang Y, Xiao X, Sun W, Wang Y, Li S, Jia X, Wang P, Hejtmancik JF, Zhang Q
J Transl Med 2024 Jan 19;22(1):75. doi: 10.1186/s12967-024-04886-5. PMID: 38243264Free PMC Article
Asano M, Yokoyama K, Oku K, Matsushita I, Kimoto K, Kubota T, Kondo H
Ophthalmic Genet 2022 Aug;43(4):508-512. Epub 2022 Apr 26 doi: 10.1080/13816810.2022.2068044. PMID: 35473494
Rossenwasser-Weiss S, Orenstein N, Zahavi A, Goldenberg-Cohen N
Curr Eye Res 2021 Jul;46(7):1051-1055. Epub 2020 Dec 9 doi: 10.1080/02713683.2020.1855661. PMID: 33295219
Rose PS, Levy HP, Liberfarb RM, Davis J, Szymko-Bennett Y, Rubin BI, Tsilou E, Griffith AJ, Francomano CA
Am J Med Genet A 2005 Oct 15;138A(3):199-207. doi: 10.1002/ajmg.a.30955. PMID: 16152640
Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI
Genet Med 2003 Jan-Feb;5(1):21-7. doi: 10.1097/00125817-200301000-00004. PMID: 12544472

Recent systematic reviews

Acke FR, Dhooge IJ, Malfait F, De Leenheer EM
Orphanet J Rare Dis 2012 Oct 30;7:84. doi: 10.1186/1750-1172-7-84. PMID: 23110709Free PMC Article

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