Avaliação da relevância clínica de fenótipos indicativos de síndromes genéticas

Abstract

It is estimated that in Brazil 13 million people are affected by some rare disease. Genetic diseases account for 80% of rare diseases and since 2015 they represent, associated with birth defects, the second cause of under-five mortality in Brazil. Nevertheless, individuals with genetic diseases still face many challenges, both in terms of access to specialized care and the availability of diagnostic tests and specific treatment. Focusing on health professionals, there is a reduced production of scientific research and insufficient academic formation for the care of these patients by general practitioners, considering the complexity and breadth of specific knowledge required. Early and accurate diagnosis of the genetic syndrome is essential for the patient. The aim of this study was to evaluate the presence of phenotypes such as “cafe-au-lait spots”, “progeroid features” and “congenital hypertrophy of the retinal pigment epithelium” for the possible diagnosis of related genetic syndromes. Four studies were developed. In the first study, a narrative review of the literature was carried out in order to identify the genetic syndromes that may be associated with cafe-au-lait spots and to assess their relevance as an indicative sign of these syndromes. A total of 60 syndromes were identified from research conducted in the OMIM database. The clinical and molecular characterization of each one was summarized and presented. In the second study, among the 60 syndromes reported in the previous study those with associated craniofacial alterations were identified and described regarding to the general and specific clinical features. In a third study, a case report of a child with a progeroid laminopathy identified as mandibuloacral dysplasia with type A lipodystrophy by molecular analysis was performed. The severe phenotype observed was associated with an unusual mutation found in the LMNA gene. In the fourth study, a large family of 95 people composed of individuals affected by or at risk for the genetic disease familial adenomatous polyposis was evaluated for the presence of the phenotypic alteration congenital hypertrophy of the retinal pigment epithelium. Ophthalmological evaluation was performed on 45 family members. The studies carried out showed that phenotypes such as “cafe-au-lait spots”, “progeroid features” and “congenital hypertrophy of the retinal pigment epithelium” are relevant as indicators of genetic conditions.