U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Stickler syndrome, type 4(STL4)

MedGen UID:
481571
Concept ID:
C3279941
Disease or Syndrome
Synonyms: COL9A1-Related Stickler Syndrome; STL4
 
Gene (location): COL9A1 (6q13)
 
Monarch Initiative: MONDO:0013590
OMIM®: 614134

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
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.

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.

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.

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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/stickler-syndrome

Clinical features

From HPO
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
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 impairment
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.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Flat capital femoral epiphysis
MedGen UID:
334001
Concept ID:
C1842155
Finding
An abnormal flattening of the proximal epiphysis of the femur.
Irregular capital femoral epiphysis
MedGen UID:
866530
Concept ID:
C4020825
Anatomical Abnormality
Irregular surface of the normally relatively smooth capital femoral epiphysis.
Flat face
MedGen UID:
342829
Concept ID:
C1853241
Finding
Absence of concavity or convexity of the face when viewed in profile.
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).
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Degenerative vitreoretinopathy
MedGen UID:
334763
Concept ID:
C1843486
Disease or Syndrome

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

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
Zechi-Ceide RM, Jesus Oliveira NA, Guion-Almeida ML, Antunes LF, Richieri-Costa A, Passos-Bueno MR
Eur J Med Genet 2008 May-Jun;51(3):183-96. Epub 2008 Jan 9 doi: 10.1016/j.ejmg.2007.12.008. PMID: 18276201
Freddi S, Savarirayan R, Bateman JF
Am J Med Genet 2000 Feb 28;90(5):398-406. PMID: 10706362

Recent clinical studies

Etiology

Linton E, Jalil A, Sergouniotis P, Moussa G, Black G, Charles S, Ivanova T
Retina 2023 Jan 1;43(1):88-93. doi: 10.1097/IAE.0000000000003634. PMID: 36165842
Naravane AV, Belin PJ, Pierce B, Quiram PA
Ophthalmic Surg Lasers Imaging Retina 2022 Jan;53(1):7-11. Epub 2022 Jan 1 doi: 10.3928/23258160-20211213-02. PMID: 34982001
Khanna S, Rodriguez SH, Blair MA, Wroblewski K, Shapiro MJ, Blair MP
Ophthalmol Retina 2022 Apr;6(4):263-267. Epub 2021 Nov 11 doi: 10.1016/j.oret.2021.11.001. PMID: 34774838
Zimmermann J, Stubbs DJ, Richards AJ, Alexander P, McNinch AM, Matta B, Snead MP
Anesth Analg 2021 Jan;132(1):202-209. doi: 10.1213/ANE.0000000000004582. PMID: 31856005Free PMC Article
Wang DD, Gao FJ, Hu FY, Li JK, Zhang SH, Xu P, Chang Q, Jiang R, Wu JH
Acta Ophthalmol 2020 Jun;98(4):e440-e446. Epub 2019 Nov 17 doi: 10.1111/aos.14302. PMID: 31736238

Diagnosis

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
Naravane AV, Belin PJ, Pierce B, Quiram PA
Ophthalmic Surg Lasers Imaging Retina 2022 Jan;53(1):7-11. Epub 2022 Jan 1 doi: 10.3928/23258160-20211213-02. PMID: 34982001
Khanna S, Rodriguez SH, Blair MA, Wroblewski K, Shapiro MJ, Blair MP
Ophthalmol Retina 2022 Apr;6(4):263-267. Epub 2021 Nov 11 doi: 10.1016/j.oret.2021.11.001. PMID: 34774838
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
Wang DD, Gao FJ, Hu FY, Li JK, Zhang SH, Xu P, Chang Q, Jiang R, Wu JH
Acta Ophthalmol 2020 Jun;98(4):e440-e446. Epub 2019 Nov 17 doi: 10.1111/aos.14302. PMID: 31736238

Prognosis

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
Zimmermann J, Stubbs DJ, Richards AJ, Alexander P, McNinch AM, Matta B, Snead MP
Anesth Analg 2021 Jan;132(1):202-209. doi: 10.1213/ANE.0000000000004582. PMID: 31856005Free PMC Article
Wang DD, Gao FJ, Hu FY, Li JK, Zhang SH, Xu P, Chang Q, Jiang R, Wu JH
Acta Ophthalmol 2020 Jun;98(4):e440-e446. Epub 2019 Nov 17 doi: 10.1111/aos.14302. PMID: 31736238
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
Couchouron T, Masson C
Joint Bone Spine 2011 Jan;78(1):45-9. Epub 2010 May 11 doi: 10.1016/j.jbspin.2010.03.012. PMID: 20462780

Clinical prediction guides

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
Zimmermann J, Stubbs DJ, Richards AJ, Alexander P, McNinch AM, Matta B, Snead MP
Anesth Analg 2021 Jan;132(1):202-209. doi: 10.1213/ANE.0000000000004582. PMID: 31856005Free PMC Article
Sergouniotis PI, Fincham GS, McNinch AM, Spickett C, Poulson AV, Richards AJ, Snead MP
Eye (Lond) 2015 Apr;29(4):475-82. Epub 2015 Jan 16 doi: 10.1038/eye.2014.334. PMID: 25592122Free PMC Article
Snead MP, Payne SJ, Barton DE, Yates JR, al-Imara L, Pope FM, Scott JD
Eye (Lond) 1994;8 ( Pt 6):609-14. doi: 10.1038/eye.1994.153. PMID: 7867814
Francomano CA, Liberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE
Genomics 1987 Dec;1(4):293-6. doi: 10.1016/0888-7543(87)90027-9. PMID: 2896625

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...