Stickler syndrome is a rare collagenopathy, caused by mutations in various genes coding for fibrillar collagens II, IX, and XI. The disorder can be subdivided into different groups, depending on the genes affected and clinical features found in patients. Ocular symptoms, such as high myopia, retinal detachments, or anomalies in the vitreous, are present in most forms of Stickler syndrome. In this case report, we present a patient with an unusual retinal phenotype. Subject of this case report is a 33-year-old woman, who was examined at the Department of Ophthalmology at Medical University of Graz. A thorough ophthalmological examination was conducted, detailed medical and family history acquired, and genetic testing performed. Best corrected visual acuity was 20/20 on both eyes; however, impaired binocular vision associated with intermittent exotropia was found. Furthermore, dilated fundoscopy showed an unusual, hypopigmented spotted retinal phenotype. Fundus autofluorescence showed multiple hyperfluorescent spots corresponding with the spotted retinal appearance. Genetic testing revealed a novel variant in the gene COL11A1. No other ocular abnormalities which are associated with COL11A1 were found. Several subtypes of Stickler syndrome have been reported in medical literature, greatly varying in clinical manifestations. Many different mutations in the gene COL11A1 have been discovered and are typically associated with Stickler syndrome type 2. To our best knowledge, this is the first report of a patient with a mutation in the COL11A1 gene presenting with a hypopigmented spotted retina.

To genetically investigate a family with a clinical and ophthalmological phenotype suggestive of Stickler syndrome (STL) and the association of molecular findings with ophthalmological, clinical characteristics, and family history. Specialized ophthalmologic evaluation using diagnostic methods such as fundoscopy, slit-lamp photography, and ocular biometry to describe the phenotypic characteristics of the index patient and family members. Genetic evaluation with genome sequencing (WGS) is to describe the genotypic characteristics of the proband and confirmation of the finding by family-specific variant sequencing (NGS). Genetic evaluation demonstrated the presence of a novel pathogenic variant NM_001854.4: C.3168+1G>A (chr1:102961865-102961865), in the intronic region that follows exon 41 of the COL11A1 in the three affected members of the family. This variant is located 1 base from the natural splicing region of this exon and consequently can impact intron removal and protein formation. As for the ophthalmological findings, the presence of low visual acuity, high axial myopia, and pathological vitreous gel with a "beaded" appearance was observed in the index case. Further clinical examination showed that other family members also had vitreous and retinal degeneration. A heterozygous novel pathogenic variant in COL11A1 was identified by complete genome sequencing in a Brazilian family with STL. Ocular examination findings photographically presented confirm the characteristic features of STL type 2.

Stickler syndrome (STL) is a collagenopathy caused by pathogenic variants in collagen-coding genes, mainly COL2A1 or COL11A1 associated with Stickler syndrome type 1 (STL1) or type 2 (STL2), respectively. Affected individuals manifest ocular, auditory, articular, and craniofacial findings in varying degrees. Previous literature and case reports describe high variability in clinical findings for patients with STL. With this case report, we broaden the clinical spectrum of the phenotype. Case report on two members of a family (mother and son) including clinical examination and genetic testing using targeted trio whole exome sequencing (trio-WES). A boy and his mother presented with microphthalmia, congenital cataract, ptosis, and moderate-to-severe sensorineural hearing loss. Trio-WES found a novel heterozygote missense variant, c.4526A>G; p(Gln1509Arg) in COL11A1 in both affected individuals. We report a previously undescribed phenotype associated with a COL11A1-variant in a mother and son, expanding the spectrum for phenotype-genotype correlation in STL2, presenting with microphthalmia, congenital cataract, and ptosis not normally associated with Stickler syndrome.

Stickler Syndrome (SS) is an inherited collagenopathy characterized by heterogenous orofacial, ocular, auditory, and skeletal abnormalities. The orofacial manifestations are variable and some patients present with cleft palate and velopharyngeal insufficiency (VPI). The incidence of VPI in SS is poorly studied and no studies have compared the incidence of VPI between Type I (COL2A1) and Type II (COL11A1) SS. The objective of this study is to compare the incidence of VPI between SS subtypes and discuss the surgical techniques used to treat them. Single-institution, retrospective chart review. Tertiary pediatric hospital. Forty-three children were diagnosed with SS between January 2003 and December 2018. Genetic testing results, genetics notes, craniofacial clinic notes, and operative reports were reviewed. Patients without genetic testing or craniofacial/otolaryngologic evaluation were excluded. Thirty-one patients met criteria and were included. Primary outcome was VPI incidence. There were 18 patients with Type I SS and 13 with Type II SS. Five (16%) patients had VPI, 2 (11%) with Type I SS compared to 3 (23%) with Type II SS (P > .05). All patients with VPI underwent surgery with either sphincter pharyngoplasty (3) or pharyngeal flap (2). Two patients with Type II SS underwent revision sphincter pharyngoplasty, with one conversion to pharyngeal flap. VPI is common for patients with SS. In this study, there was no significant difference in the incidence of VPI between SS subtypes. Future studies are needed to confirm these findings, which could be important for patient counseling and treatment planning.

Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration. An ophthalmic assessment revealed that there was bilateral vitreal degeneration, macrophthalmos, and spherophakia in addition to cataracts. Follow-up consultations revealed cataract progression, retinal detachment, uveitis and secondary glaucoma. Whole genome sequence filtered variants private to the case, shared with another Old English Sheepdog genome and predicted to be deleterious were genotyped in an initial cohort of six Old English Sheepdogs (three affected by multiocular defect and three control dogs without evidence of inherited eye disease). Only one of the twenty-two variants segregated correctly with multiocular defect. The variant is a single nucleotide substitution, located in the collagen-type gene COL11A1, c.1775T>C, that causes an amino acid change, p.Phe1592Ser. Genotyping of an additional 14 Old English Sheepdogs affected by multiocular defect revealed a dominant mode of inheritance with four cases heterozygous for the variant. Further genotyping of hereditary cataract-affected Old English Sheepdogs revealed segregation of the variant in eight out of nine dogs. In humans, variants in the COL11A1 gene are associated with Stickler syndrome type II, also dominantly inherited.