Stickler Syndrome Precision Panel
Stickler Syndrome (SS), also known as hereditary arthroophthalmopathy belongs to the group of connective tissue disorders together with Marshall syndrome, and so have overlapping characteristics.
Overview
- Stickler Syndrome (SS), also known as hereditary arthroophthalmopathy belongs to the group of connective tissue disorders together with Marshall syndrome, and so have overlapping characteristics. It is caused by mutations of genes in charge of the assembly of collagen. Since collagen is a major component of cartilage, vitreous and nucleus pulposus the clinical manifestations will affect these structures. Affected individuals are at significantly increased risk for retinal detachment and blindness, and early detection and diagnosis are critical in improving visual outcomes of these patients. The mode of inheritance varies from autosomal dominant, recessive and X-linked.
- The Igenomix Stickler Syndrome Precision Panel can be used to make a directed and accurate diagnosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
- The Igenomix Stickler Syndrome Precision Panel is indicated for those patients with a clinical diagnosis or suspicion with or without the following manifestations:
- Orofacial abnormalities: midfacial underdevelopment and cleft palate
- Ophthalmologic abnormalities: myopia, cataract, retinal detachment
- Hearing loss
- Precocious arthritis
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team in the form of surgical repair of orofacial abnormalities, retinal detachment, hearing and visual aids and symptomatic medical treatment for arthropathy. Early and continuous ophthalmologic examination follow-up to prevent further complications.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
Genes & Diseases
See all genes and diseases
| GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
| ACTA2 | Aortic Aneurysm, Moyamoya Disease, Multisystemic Smooth Muscle Dysfunction Syndrome |
AD |
100 |
88 of 88 |
| ADAMTS2 | Ehlers-Danlos Syndrome |
AR |
95.99 |
9 of 10 |
| AEBP1 | Ehlers-Danlos Syndrome |
AR |
99.35 |
9 of 9 |
| ALDH18A1 | Cutis Laxa, Corneal Clouding, Mental Retardation, Spastic Paraplegia, De Barsy Syndrome |
AD,AR |
100 |
39 of 40 |
| ATP6V0A2 | Cutis Laxa, Wrinkly Skin Syndrome |
AR |
99.99 |
55 of 55 |
| ATP6V1E1 | Cutis Laxa |
AR |
100 |
2 of 2 |
| ATP7A | Cutis Laxa, Menkes Disease, Spinal Muscular Atrophy, Occipital Horn Syndrome |
X,XR,G |
99.83 |
– |
| B3GALT6 | Ehlers-Danlos Syndrome, Spondyloe- pimetaphyseal Dysplasia, Joint Laxity |
AR |
65.09 |
24 of 39 |
| B3GAT3 | Multiple Joint Dislocations, Short Stature, Craniofacial Dysmorphism |
AR |
99.86 |
15 of 15 |
| B4GALT7 | Ehlers-Danlos Syndrome |
AR |
99.92 |
11 of 11 |
| BGN | Meester-Loeys Syndrome, Spondylo- epimetaphyseal Dysplasia |
X,XR,G |
99.87 |
– |
| CBS | Homocystinuria |
AR |
99.98 |
192 of 194 |
| CHST14 | Ehlers-Danlos Syndrome |
AR |
97.7 |
21 of 22 |
| COL11A1 | Deafness, Fibrochondrogenesis, Marshall Syndrome, Stickler Syndrome, Myopia, Midfacial Retrusion, Sensorineural Hearing Loss, Rhizomelic Dysplasia |
AD,AR |
100 |
104 of 106 |
| COL11A2 | Deafness, Fibrochondrogenesis, Otospondylo- megaepiphyseal Dysplasia, Stickler Syndrome |
AD,AR |
99.98 |
58 of 58 |
| COL12A1 | Bethlem Myopathy, Ullrich Congenital Muscular Dystrophy, Ehlers-Danlos Syndrome |
AD |
99.97 |
18 of 19 |
| COL1A1 | Caffey Disease, Ehlers-Danlos Syndrome, Osteogenesis Imperfecta, Osteoporosis, Dermatofibrosarcoma Protuberans |
AD |
99.98 |
1156 of 1159 |
| COL1A2 | Ehlers-Danlos Syndrome, Osteogenesis Imperfecta, Osteoporosis |
AD,AR |
100 |
576 of 581 |
| COL2A1 | Achondrogenesis, Avascular Necrosis Of Femoral Head, Czech Dysplasia, Epiphyseal Dysplasia, Kniest Dysplasia, Legg-Calve- Perthes Disease, Osteoarthritis, Stickler Syndrome, Dysspondylo- enchondromatosis, Platyspondylic Dysplasia, Spondylo- epimetaphyseal Dysplasia |
AD,MU |
100 |
583 of 583 |
| COL3A1 | Ehlers-Danlos Syndrome, Polymicrogyria, Acrogeria, Cerebral Saccular Aneurysm |
AD,AR |
100 |
676 of 676 |
| COL4A1 | Angiopathy, Nephropathy, Aneurysms, Microangiopathy, Leukoen- cephalopathy, Porencephaly, Hanac Syndrome, Walker-Warburg Syndrome |
AD |
99.99 |
173 of 173 |
| COL5A1 | Ehlers-Danlos Syndrome |
AD |
99.08 |
191 of 195 |
| COL5A2 | Ehlers-Danlos Syndrome |
AD |
100 |
45 of 45 |
| COL9A1 | Epiphyseal Dysplasia, Stickler Syndrome |
AD,AR |
99.98 |
8 of 8 |
| COL9A2 | Epiphyseal Dysplasia, Stickler Syndrome |
AD,AR |
100 |
16 of 16 |
| COL9A3 | Epiphyseal Dysplasia, Stickler Syndrome |
AD |
99.98 |
20 of 20 |
| DSE | Ehlers-Danlos Syndrome |
AR |
99.94 |
3 of 3 |
| EFEMP2 | Cutis Laxa |
AR |
99.99 |
17 of 17 |
| ELN | Cutis Laxa, Supravalvular Aortic Stenosis, Williams- Beuren Syndrome, Thoracic Aortic Aneurysm |
AD |
99.99 |
95 of 96 |
| FBLN5 | Cutis Laxa, Neuropathy, Macular Degeneration |
AD,AR |
97.43 |
23 of 23 |
| FBN1 | Acromicric Dysplasia, Ectopia Lentis, Geleophysic Dysplasia, Marfan Syndrome, Mass Syndrome, Stiff Skin Syndrome, Weill-Marchesani Syndrome, Thoracic Aortic Aneurysm, Shprintzen– Goldberg Syndrome |
AD |
100 |
2836 of 2845 |
| FBN2 | Contractural Arachnodactyly, Macular Degeneration |
AD |
100 |
115 of 115 |
| FKBP14 | Ehlers-Danlos Syndrome, Myopathy, Hearing Loss |
AR |
99.98 |
7 of 8 |
| FLNA | Cardiac Valvular Dysplasia, Fg Syndrome, Frontometaphyseal Dysplasia, Heterotopia, Intestinal Pseudoobstruction, Melnick-Needles Syndrome, Otopalatodigital Syndrome, Terminal Osseous Dysplasia, Congenital Short Bowel Syndrome, Ehlers-Danlos Syndrome |
X,XR,XD,G |
100 |
– |
| LOX | Aortic Aneurysm |
AD |
95.47 |
8 of 8 |
| LOXL3 | Stickler Syndrome |
– |
99.97 |
7 of 7 |
| LRP2 | Donnai-Barrow Syndrome |
AR |
99.99 |
58 of 58 |
| LTBP4 | Cutis Laxa, Duchenne Muscular Dystrophy |
AR |
97.45 |
27 of 27 |
| MAT2A | Thoracic Aortic Aneurysm, Aortic Dissection |
– |
100 |
3 of 3 |
| MED12 | Lujan- Fryns Syndrome, Ohdo Syndrome, Opitz-Kaveggia Syndrome, Blepharophimosis, Intellectual Disability Syndrome, Fg Syndrome |
X,XR,G |
100 |
– |
| MFAP5 | Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
100 |
3 of 3 |
| MYH11 | Thoracic Aortic Aneurysm, Aortic Dissection, Megacystis, Microcolon, Intestinal Hypoperistalsis |
AD |
100 |
67 of 67 |
| MYLK | Thoracic Aortic Aneurysm, Aortic Dissection, Megacystis, Microcolon, Intestinal Hypoperistalsis |
AD |
99.95 |
50 of 50 |
| NOTCH1 | Adams-Oliver Syndrome, Aortic Valve Disease |
AD |
99.83 |
178 of 179 |
| PLOD1 | Ehlers-Danlos Syndrome |
AR |
100 |
36 of 36 |
| PRDM5 | Brittle Cornea Syndrome |
AR |
99.86 |
13 of 13 |
| PRKG1 | Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
99.93 |
6 of 6 |
| PYCR1 | Cutis Laxa, Geroderma Osteodysplastica |
AR |
100 |
44 of 44 |
| RIN2 | Macrocephaly, Alopecia, Cutis Laxa, Scoliosis, Rin2 Syndrome |
AR | 99.6 | 4 of 4 |
| SKI | 1p36 Deletion Syndrome, Shprintzen– Goldberg Syndrome |
AD |
99.66 |
39 of 39 |
| SLC2A10 | Arterial Tortuosity Syndrome |
AR |
100 |
35 of 35 |
| SLC39A13 | Ehlers- Danlos Syndrome |
AR |
100 |
9 of 9 |
| SMAD2 | Osteopoikilosis |
– |
100 |
19 of 19 |
| SMAD3 | Loeys-Dietz Syndrome, Aneurysm- Osteoarthritis Syndrome, Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
100 |
128 of 128 |
| SMAD4 | Polyposis Syndrome, Hemorrhagic Telangiectasia, Myhre Syndrome, Pancreatic Cancer, Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
99.56 |
136 of 136 |
| TAB2 | Congenital Heart Defects, Polyvalvular Heart Disease Syndrome |
AD |
99 |
13 of 13 |
| TGFB2 | Loeys-Dietz Syndrome, Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
99.9 |
41 of 44 |
| TGFB3 | Right Ventricular Dysplasia, Loeys-Dietz Syndrome, Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
100 |
34 of 35 |
| TGFBR1 | Loeys-Dietz Syndrome, Self-Healing Squamous Epithelioma, Thoracic Aortic Aneurysm, Aortic Dissection |
AD |
94 |
96 of 100 |
| TGFBR2 | Colorectal Cancer, Esophageal Cancer, Loeys-Dietz Syndrome, Familial Thoracic Aortic Aneurysm, Aortic Dissection, Lynch Syndrome |
AD |
99.9 |
165 of 166 |
| TNXB | Vesicoureteral Reflux, Ehlers-Danlos Syndrome |
AD,AR |
92.75 |
29 of 33 |
| VCAN | Wagner Syndrome |
AD |
99.91 |
11 of 21 |
| ZNF469 | Brittle Cornea Syndrome |
AR |
99.91 |
79 of 79 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial
** HGMD: Number of clinically relevant mutations according to HGMD
References
Cervelli, V., Bottini, D., Grimaldi, M., Gentile, P., Caruso, R., & Gravante, G. (2008). The Stickler syndrome. A genetic disease with clinical implications for the plastic surgeon. Journal Of Plastic, Reconstructive & Aesthetic Surgery, 61(8), 987-988. doi: 10.1016/j.bjps.2007.11.059
Richards, A., McNinch, A., Martin, H., Oakhill, K., Rai, H., & Waller, S. et al. (2010). Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Human Mutation, 31(6), E1461-E1471. doi: 10.1002/humu.21257
Stickler Syndrome. (2021). Retrieved 31 March 2021, from http://www.ncbi.nlm.nih.gov.ezp-prod1.hul.harvard.edu/books/NBK1302/
Boothe, M., Morris, R., & Robin, N. (2020). Stickler Syndrome: A Review of Clinical Manifestations and the Genetics Evaluation. Journal of personalized medicine, 10(3), 105. https://doi.org/10.3390/jpm10030105
Robin, N. H., Moran, R. T., & Ala-Kokko, L. (2000). Stickler Syndrome. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
Rishi, P., Maheshwari, A., & Rishi, E. (2015). Stickler syndrome. Indian journal of ophthalmology, 63(7), 614–615. https://doi.org/10.4103/0301-4738.167114
Aylward, B., daCruz, L., Ezra, E., Sullivan, P., MacLaren, R. E., Charteris, D., Gregor, Z., Bainbridge, J., & Minihan, M. (2008). Stickler syndrome. Ophthalmology, 115(9), 1636–1638. https://doi.org/10.1016/j.ophtha.2008.04.018
