RESUMEN
Czech dysplasia is an autosomal dominant type 2 collagenopathy that is caused by heterozygosity for the recurrent p.(Arg275Cys) COL2A1 variant. Affected individuals usually present with skeletal abnormalities such as metatarsal hypoplasia of the third and fourth toes and early-onset arthropathy, as well as hearing loss. To date, no ophthalmic findings have been reported in patients with Czech dysplasia even though COL2A1 has been implicated in other ocular conditions such as type 1 Stickler syndrome. For the first time, we report the ocular findings in four families with Czech dysplasia, including type 1 vitreous anomaly, hypoplastic vitreous, retinal tears, and significant refractive error. These novel ocular findings expand the phenotype associated with Czech dysplasia and may aid clinicians as an additional diagnostic feature. Patients with congenital abnormalities of vitreous gel architecture have an increased risk of retinal detachment, and as such, patients may benefit from prophylaxis. Considering that many of the patients did not report any ocular symptoms, vitreous phenotyping is of key importance in identifying the need for counseling with regard to prophylaxis.
Asunto(s)
Artritis , Enfermedades del Tejido Conjuntivo , Pérdida Auditiva Sensorineural , Osteocondrodisplasias , Desprendimiento de Retina , Dedos del Pie/anomalías , Humanos , Enfermedades del Tejido Conjuntivo/genética , Pérdida Auditiva Sensorineural/genética , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/genética , Artritis/genética , Mutación , Colágeno Tipo II/genética , LinajeRESUMEN
This clinical report describes a family with both Marfan and ocular-only Stickler syndromes. We report 2 cases of ocular-only Stickler syndrome and 2 cases of Marfan syndrome concurrent with ocular-only Stickler syndrome. Type 1 Stickler syndrome and Marfan syndrome share many clinical similarities, and it can be difficult to differentiate them solely based on clinical presentation. Vitreous phenotyping allows for the identification of vitreous anomalies pathognomonic of Stickler syndrome, which can guide future gene sequencing. Having the accurate diagnosis of Marfan or type 1 Stickler syndrome is important, as patients with type 1 Stickler syndrome have higher rates of retinal detachment and will benefit from prophylaxis.
Asunto(s)
Enfermedades Hereditarias del Ojo , Pérdida Auditiva Sensorineural , Síndrome de Marfan , Desprendimiento de Retina , Humanos , Desprendimiento de Retina/diagnóstico , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/genética , Pérdida Auditiva Sensorineural/diagnóstico , Enfermedades Hereditarias del Ojo/genética , Fenotipo , Biomarcadores , Mutación , LinajeRESUMEN
The Stickler syndromes are a group of genetic connective tissue disorders associated with an increased risk of rhegmatogenous retinal detachment, deafness, cleft palate, and premature arthritis. This review article focuses on the molecular genetics of the autosomal dominant forms of the disease. Pathogenic variants in COL2A1 causing Stickler syndrome usually result in haploinsufficiency of the protein, whereas pathogenic variants of type XI collagen more usually exert dominant negative effects. The severity of the disease phenotype is thus dependent on the location and nature of the mutation, as well as the normal developmental role of the respective protein.