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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
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.

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.

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.

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
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
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 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.
Coxa vara
MedGen UID:
1790477
Concept ID:
C5551440
Anatomical Abnormality
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Intervertebral space narrowing
MedGen UID:
78101
Concept ID:
C0263870
Finding
Decreased height of the intervertebral disk.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Short femoral neck
MedGen UID:
373033
Concept ID:
C1836184
Finding
An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Flat capital femoral epiphysis
MedGen UID:
334001
Concept ID:
C1842155
Finding
An abnormal flattening of the proximal epiphysis of the femur.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Irregular femoral epiphysis
MedGen UID:
340592
Concept ID:
C1850658
Finding
Hypoplastic iliac wing
MedGen UID:
351279
Concept ID:
C1865027
Anatomical Abnormality
Underdevelopment of the ilium ala.
Irregular capital femoral epiphysis
MedGen UID:
866530
Concept ID:
C4020825
Anatomical Abnormality
Irregular surface of the normally relatively smooth capital femoral epiphysis.
Hypernasal speech
MedGen UID:
107884
Concept ID:
C0566620
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Hyperplasia of midface
MedGen UID:
451009
Concept ID:
C0240309
Anatomical Abnormality
Abnormally anterior positioning of the infraorbital and perialar regions, or increased convexity of the face, or increased nasolabial angle. The midface includes the maxilla, the cheeks, the zygomas, and the infraorbital and perialar regions of the face
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
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).
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within 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.
Rhegmatogenous retinal detachment
MedGen UID:
489829
Concept ID:
C0271055
Finding
A type of retinal detachment associated with a retinal tear, that is, with a break in the retina that allows fluid to pass from the vitreous space into the subretinal space between the sensory retina and the retinal pigment epithelium.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Chorioretinal degeneration
MedGen UID:
99273
Concept ID:
C0521683
Pathologic Function
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

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Retina 2023 Jan 1;43(1):88-93. doi: 10.1097/IAE.0000000000003634. PMID: 36165842
Naravane AV, Belin PJ, Pierce B, Quiram PA
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Ophthalmol Retina 2022 Apr;6(4):263-267. Epub 2021 Nov 11 doi: 10.1016/j.oret.2021.11.001. PMID: 34774838
Wang DD, Gao FJ, Hu FY, Li JK, Zhang SH, Xu P, Chang Q, Jiang R, Wu JH
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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
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Prognosis

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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
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

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
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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
Nixon TRW, Richards A, Towns LK, Fuller G, Abbs S, Alexander P, McNinch A, Sandford RN, Snead MP
Eur J Hum Genet 2019 Mar;27(3):369-377. Epub 2018 Dec 19 doi: 10.1038/s41431-018-0316-y. PMID: 30568244Free 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

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