Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation

Abstract

Background Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients. Methods Herein, we report a case of an 8‐year‐ old child with Stickler Syndrome, presenting with early‐onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene. Results A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing. Conclusion We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early‐onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene‐related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease.

Genetic testing in four Indian families with suspected Stickler syndrome

“…COL11A1 mutations were associated with vitreoretinal anomalies and sensorineural hearing loss in Stickler syndrome patients[ 13 ]; in our study, we did not record similar history in family IV harboring COL11A1 gene mutations. Screening of controls are however required to prove the pathogenicity status of the observed VUS in COL11A1 gene and to confirm the molecular classification.…”

Comparing Gene Panels for Non-Retinal Indications: A Systematic Review

“…It can also be beneficial in nonsyndromic cases to help with counseling and other associated eye conditions, e.g., certain genes are associated with glaucoma and cataracts, such as GJA8 [ 22 ] (tested in five of five panels). Other conditions, such as COL11A1 (included in four of five panels) can be associated with cataracts and Stickler syndrome with an increased risk of retinal detachment [ 23 , 24 , 25 ].…”

“…Each co-author listed the most common indications for which they ordered genetic testing and the most common panels they ordered for specific indications. The most common genetic causes for each disease process that merited genetic testing were recorded [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Whether or not these genes were analyzed by the corresponding panels was then documented.…”

An Emergent Nexus between Striae and Thoracic Aortic Dissection

“…Club foot and cleft palate, which are associated with LDS [ 13 ], were identified in one patient each. Neither patient had arterial tortuosity, which is common in LDS, and the cleft palate was likely due to the diagnosis of Stickler syndrome [ 14 ]. These results support a low level of suspicion for undiagnosed MFS or LDS in striae cases who did not have clinical genetic testing.…”