RESUMO
Persistent fetal vasculature (PFV) is most often a condition of unknown cause. It represents persisting elements of fetal ocular vessels including the hyaloid arterial network. Protein C is a vitamin K-dependent serine protease, which regulates coagulation. Deficiency of protein C leads to a prothrombotic state. We report the case of a male infant born at 34 weeks gestation to non-consanguineous parents. Ophthalmic examination found bilateral PFV, microphthalmia and vitreoretinal dysplasia. He also suffered bilateral renal vein thrombosis and purpura fulminans and was diagnosed with severe protein C deficiency. Genetic analysis of the PROC gene revealed two separate pathogenic mutations, confirming compound heterozygote status. Both parents were found to be heterozygous. While ocular manifestations (commonly haemorrhages) are often seen in protein C-deficient patients, a search of the literature reveals very few recorded cases of PFV in severe protein C deficiency. We hypothesise that protein C deficiency was the cause of PFV in this patient. Intraocular thrombotic events in utero could affect the normal development of ocular vessels and lead to persistent elements of fetal vasculature in the eye. Consideration should be given to the possibility of protein C deficiency in patients presenting with PFV, particularly if bilateral.
Assuntos
Predisposição Genética para Doença/genética , Proteínas de Choque Térmico/genética , Padrões de Herança/genética , Espasticidade Muscular/genética , Degenerações Espinocerebelares/genética , Adulto , Atrofia/genética , Atrofia/patologia , Tronco Encefálico/patologia , Tronco Encefálico/fisiopatologia , Cerebelo/metabolismo , Cerebelo/patologia , Cerebelo/fisiopatologia , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Genes Dominantes/genética , Genes Recessivos/genética , Testes Genéticos , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/genética , Espasticidade Muscular/fisiopatologia , Mutação/genética , Fibras Nervosas Mielinizadas/patologia , Linhagem , Fenótipo , Degenerações Espinocerebelares/fisiopatologia , Adulto JovemRESUMO
Mutations in the gene encoding fibrillin 1 (FBN1) cause Marfan syndrome (MFS), and related connective tissue disorders. The disease spectrum is wide and while many genotype-phenotype correlations have been reported, few have been consistent. In this study FBN1 was analyzed in 113 patients with MFS or Marfan-like features. Fifty-three mutations were identified in 52 individuals, 41 of which were novel. The mutations comprised 26 missense, 11 splice site, 7 frameshift, 6 nonsense, 1 in-frame deletion, and 2 whole exon deletions. In common with previous studies, genotype-phenotype analysis showed that a FBN1 mutation was more likely to be identified in patients fulfilling Ghent criteria (P = 0.005) and in those who had ectopia lentis (EL) (P < 0.0001). Other previously reported genotype-phenotype correlations were also considered and a new inverse association between a mutation in exons 59-65, and EL emerged (P = 0.002).
