1 - Serviço de Genética Médica, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
2 - Unidade de Genética Molecular, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal; Unidade Multidisciplinar de Investigação Biomédica, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto (UMIB/ICBAS/UP), Porto, Portugal
3 - Serviço de Oftalmologia, Hospital Nélio Mendonça, Funchal, Portugal
4 - Consulta de Genética Médica, Hospital Nélio Mendonça, Funchal, Portugal
- 25th Annual Virtual Meeting Sociedade Portuguesa de Genética Humana, 18-19 de Novembro, virtual meeting. Sob a forma de poster.
Resumo:
Introduction: Traboulsi syndrome (TS) or Facial Dysmorphism, Lens dislocation, Anterior‑segment abnormalities and spontaneous filtering Blebs syndrome (#601552) is a syndromic form of ectopia lens. It is characterized by ocular features (spontaneous lens (sub)luxation, subconjunctival bleb formation, shallow anterior chamber, iridocorneal adhesions, glaucoma, corneal edema, scleral thinning and decreased visual acuity), craniofacial dysmorphisms, skeletal signs, hypermobile joints and cardiac involvement. TS results from biallelic pathogenic variants in the ASPH gene, which encodes an aspartate beta-hydroxylase that hydroxylates the aspartic acid and asparagine in epidermal growth factor-like domains of several proteins. So far, 19 cases were reported in the literature.
Case report: We report a 25-year-old male with a severe ophthalmopathy. Third child of apparent non-consanguineous healthy parents. He has a brother with similar phenotypic features. First evaluated with 8 years at an ophthalmology appointment with high myopia that progressed through the years to bilateral ectopia and subluxation of crystalline lenses and amblyopia of the left eye. At our observation he showed facial dysmorphisms, elongated face, prominent nose with a convex nasal bridge, malar hypoplasia, malocclusion and retrognathia. Due to persistent lumbar arthralgias an MRI was performed but no structural changes were identified. Echocardiogram revealed a mitral valve prolapse. Exome sequencing was performed and identified a homozygous splice site variant in ASPH: c.1765-1G>A, classified as pathogenic, that explains our patient phenotype and supported the diagnosis of TS. Segregation testing is ongoing.
Conclusion: TS shows many overlapping features with other connective tissues disorders, such as Marfan syndrome, and should be considered as a differential diagnosis. Also, this case contributes to the expansion of TS genotype with a novel splice site pathogenic variant in the ASPH gene. From a practical standpoint, it provided an appropriated genetic counselling and a better surveillance to this patient and family.
Palavras Chave: ASPH gene, bilateral ectopia, dysmorphisms, ophthalmopathy, Traboulsi syndrome