Stickler syndrome – lessons from a national cohort

Abstract

In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families. Using a combination of accurate phenotyping and molecular genetic analysis it is possible to identify the underlying genetic mutation in over 95% of cases including those with deep intronic mutations likely to be missed by conventional exome panel analysis and which require whole gene sequencing and supplementary functional analysis to confirm pathogenicity. The vast majority that presents to ophthalmologists will be from one of three autosomal dominant sub-groups with a high associated risk of retinal detachment but the diagnosis is often overlooked, especially in adults. In contrast to many other blinding retinal conditions, blindness through giant retinal tear detachment particularly in children is largely preventable provided these high-risk groups are identified and appropriate evidence-based prophylaxis offered. This article summarises ten selected briefcase histories from the national dataset with key learning points from each.

Dominant Stickler Syndrome

“…A classification of the subgroups of Stickler syndrome based on vitreous phenotypes has developed over the last 20 years and has proven to be a reliable method of both diagnosing Stickler syndrome and guiding molecular analysis [ 12 ]. More recently, cases of Stickler syndrome associated with pathogenic variants in an increasing number of gene loci have been reported, resulting in the identification of at least 10 different subgroups of Stickler syndrome associated with pathogenic variants in 8 distinct genes (with 5 of these subgroups falling under the category of autosomal dominant) ( Table 1 ) [ 2 , 13 ]. This article reviews the autosomal dominant forms of Stickler syndrome, which account for the majority of patients that present to clinicians.…”

“…The diagnosis of Stickler syndrome should be considered in any of the following [ 13 ]: Infants with a history of congenital myopia in association with deafness Infants born with cleft palate or Pierre Robin Sequence in association with myopia Infants with joint hypermobility and/or epiphyseal dysplasia in association with myopia Individuals suffering rhegmatogenous retinal detachment with a family history of rhegmatogenous retinal detachment. …”

“…( a ) Membranous congenital vitreous anomaly, ( b ) Beaded congenital vitreous anomaly. Reproduced with permission from Snead et al [ 13 ].…”

“…( Bottom ) Giant Retinal Tear in child with undiagnosed type 1 Stickler syndrome. Reproduced with permission from Snead et al [ 13 ].…”

Quality of Life in Children and Adolescents with Stickler Syndrome in Spain

“…Moreover, this was the first study to compile data on the quality of life in children with SS. Other studies in the literature made classifications based on genetics and radiological findings in SS [ 34 , 35 , 36 ], leaving aside the analysis of psychosocial factors and quality of life.…”