title: Vitreous phenotype: a key diagnostic sign in Stickler syndrome types 1 and 2 complicated by double heterozygosity.
abstract: We describe the clinical findings in two patients with double heterozygosity, both involving Stickler syndrome. In case 1, the proposita had Albright hereditary osteodystrophy which was inherited from her mother and type 1 Stickler syndrome which was a new mutation. The combination of manifestations from the two syndromes had resulted in initial diagnostic confusion. Diagnosis of the latter syndrome was made only following ophthalmic examination which documented the presence of a membranous vitreous anomaly characteristic of type 1 Stickler syndrome. Subsequent confirmation was achieved by mutation analysis of the COL2A1 gene. The propositus in case 2 inherited Treacher Collins syndrome paternally and type 2 Stickler syndrome maternally. The overlap of facial anomalies may have resulted in a more severe phenotype for the patient. The diagnosis of Stickler syndrome in the propositus was confirmed initially by vitreous assessment and later by demonstration of mutation in the COL11A1 gene. These two patients highlight the key role of vitreous examination and vitreoretinal phenotyping in the differential diagnosis of Stickler syndrome and its subtypes in cases where the clinical picture is complicated by double heterozygosity.
authors.affiliation: Vitreoretinal Service, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Ang
authors.forename: Tsiang
authors.initials: T
authors.lastname: Ung
authors.forename: Narman
authors.initials: N
authors.lastname: Puvanachandra
authors.forename: Louise
authors.initials: L
authors.lastname: Wilson
authors.forename: Frances
authors.initials: F
authors.lastname: Howard
authors.forename: Michael
authors.initials: M
authors.lastname: Ryalls
authors.forename: Allan
authors.initials: A
authors.lastname: Richards
authors.forename: Sarah
authors.initials: S
authors.lastname: Meredith
authors.forename: Maureen
authors.initials: M
authors.lastname: Laidlaw
authors.forename: Arabella
authors.initials: A
authors.lastname: Poulson
authors.forename: John
authors.initials: J
authors.lastname: Scott
authors.forename: Martin
authors.initials: M
authors.lastname: Snead
mesh_terms: D000015:Abnormalities, Multiple / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D002675:Child, Preschool; D002864:Chromogranins; D024043:Collagen Type II / Q000235:genetics; D003240:Connective Tissue Diseases / Q000473:pathology*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D015785:Eye Diseases, Hereditary / Q000473:pathology*; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D013577:Syndrome; D014822:Vitreous Body / Q000473:pathology*
chemical_list: C499177:COL2A1 protein, human; D002864:Chromogranins; D024043:Collagen Type II; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs