Stickler syndrome - lessons from a national cohort.

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.

Stickler syndrome in children: a radiological review.

AIM: To review the radiological findings of the largest cohort to date of paediatric patients with Stickler syndrome, all with confirmed molecular genetic analysis and sub-typing. PATIENTS AND METHODS: It is understood that the National Health Service (NHS) commissioned service at Addenbrookes Hospital, Cambridge, UK has the largest cohort of Stickler syndrome patients in the paediatric age group worldwide with 240 registered children. Fifty-nine were assessed radiologically and for their genotypes. These radiographs were reviewed and 74 knee, 45 pelvic, and 47 spinal examinations were evaluated. RESULTS: Radiological features were noted in 45.9% of knee radiographs, 11.1% of pelvic radiographs, and 42.6% of spinal radiographs. The findings were reviewed in the light of each patient's specific genetic Stickler syndrome subtype. CONCLUSION: The prevalence of orthopaedic abnormalities overall in the present series is substantially below those published in previous smaller case series. This would support the more recent findings of an array of ocular only phenotypes of Stickler syndrome described in the literature.

Ophthalmic and molecular genetic findings in Kniest dysplasia.

PURPOSE: To study the variability of the ophthalmic phenotype in Kniest dysplasia. Kniest dysplasia is an inherited disorder associated with defects in type II collagen and characterised by short-trunked dwarfism, kyphoscoliosis, and enlarged joints with restricted mobility. Other features include marked hand arthropathy, cleft palate, hearing loss, and ocular abnormalities (myopia, abnormal vitreous, and high risk of developing retinal detachment). METHODS: Data from eight unrelated individuals with a clinical and molecular diagnosis of Kniest dysplasia are reported. Clinical assessment included an audiogram and ophthalmological examination in all but one patient who died in the immediate postnatal period. Sanger sequencing of the COL2A1 gene was performed. RESULTS: Six of the seven patients tested were high myopes with one patient being an emmetrope. Bilateral quandratic cataracts and subluxed lenses were noted in one subject. Variable but abnormal vitreous architecture was observed in all seven individuals tested. Six of the seven patients had significant hearing impairment and five of the seven patients exhibited clefting abnormalities. One patient had bilateral retinal detachments in his twenties. Six dominant disease-causing COL2A1 variants were detected. In three cases, testing of parental samples revealed that the disease-causing variant was not present in either parent. CONCLUSION: The ophthalmic features in Kniest dysplasia are very similar to those in other disorders of type II collagen such as Stickler syndrome. It is likely that different type II collagenopathies have a similar level of ocular morbidity and regular ophthalmologic examination is recommended. Kniest dysplasia is associated with heterozygous COL2A1 mutations that are frequently de novo.

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

The entity described by Gunnar Stickler, which included hereditary arthro-ophthalmopathy associated with retinal detachment, has recently been recognised to consist of a number of subgroups, which might now more correctly be referred to as the Stickler syndromes. They are the most common clinical manifestation of the type II/XI collagenopathies and are the most common cause of inherited rhegmatogenous retinal detachment. This review article is intended to provide the ophthalmologist with an update on current research, subgroups, and their diagnosis together with a brief overview of allied conditions to be considered in the clinical differential diagnosis. We highlight the recently identified subgroups with a high risk of retinal detachment but with minimal or absent systemic involvement--a particularly important group for the ophthalmologist to identify.