Vitreous phenotype: A key diagnostic sign in Stickler syndrome types 1 and 2 complicated by double heterozygosity

• Published in: American journal of medical genetics. Part A 2007-03, Vol.143A (6), p.604-607
• Main Authors: Ang, Alan, Ung, Tsiang, Puvanachandra, Narman, Wilson, Louise, Howard, Frances, Ryalls, Michael, Richards, Allan, Meredith, Sarah, Laidlaw, Maureen, Poulson, Arabella, Scott, John, Snead, Martin
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - classification; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; Adolescent; Albright hereditary osteodystrophy; Biological and medical sciences; Child, Preschool; Chromogranins; Collagen Type II - genetics; Connective Tissue Diseases - pathology; Diagnosis, Differential; Diseases of the osteoarticular system; DNA Mutational Analysis; double heterozygosity; Endocrinopathies; Eye Diseases, Hereditary - pathology; Female; GTP-Binding Protein alpha Subunits, Gs - genetics; Heterozygote; Humans; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Mutation; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Parathyroids. Parafollicular cells. Cholecalciferol. Phosphocalcic homeostasis (diseases); Phenotype; Stickler; Syndrome; Treacher Collins syndrome; vitreous; Vitreous Body - pathology
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31527

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. © 2007 Wiley‐Liss, Inc.