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.

Hearing impairment in Stickler syndrome: a systematic review

“…Seven papers that fulfilled the inclusion criteria were withheld because of different reasons. Five of them contained data of patients being described more thoroughly in another paper [6,7,58-60], one reported a patient suffering from a second genetic disorder that could as well result in hearing loss [61], and hearing impairment in another one was unclear [62]. Quality of the included papers was assessed (Additional file 1: Table S1), but none of them were rejected based on quality properties alone, in order to obtain a large population in which it is possible to draw firm conclusions.…”

Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist

“…37 (v) Compound Heterozygosity. 38 In addition to assisting the clinical diagnosis, the diagnostic protocol depicted in Figure 2 assists and directs mutation analysis substantially improving COL2A1 analysis resulting in a 95% positive pick-up rate. 15,39 The advances currently being made in sequencing technologies, so-called next-generation sequencing, may in future make it more economically viable to sequence and analyse all candidate genes simultaneously; however, at present, the vitreous phenotyping before molecular analysis greatly increases the efficiency of mutation detection.…”

Targeted next‑generation sequencing identifies two novel COL2A1 gene mutations in Stickler syndrome with bilateral retinal detachment

“…The diagnostic criteria for Stickler syndrome have not been well-established ( 5 , 10 ). Adult patients diagnosed with Stickler syndrome typically do not present with typical facial anomalies as children ( 41 ).…”

“…Stickler syndrome is caused by mutations in collagen genes during fetal development, and can be divided into various subtypes based on the clinical manifestations and underlying genetic mutations ( 10 ). The most common form, Type 1 Stickler syndrome, is caused by a collagen type II α1 chain (COL2A1) mutation (OMIM no.…”