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Abstract(s)
A Síndrome de Deleção 22q11.2 é a doença genética com microdeleção mais frequente a nível mundial, e engloba as anteriormente designadas síndromes de DiGeorge, velocardiofacial, entre outras, por apresentarem uma causa genética comum – a deleção no braço longo do cromossoma 22, região 11.2. Esta origina defeitos no desenvolvimento embrionário, condicionando um quadro clínico multissistémico, com elevada variabilidade fenotípica, razão pela qual é frequentemente subdiagnosticada. Embora a tríade clássica da doença seja caracterizada por anomalias cardíacas cono-truncais, hipoplasia tímica e hipocalcémia, o conhecimento crescente acerca de outras possíveis manifestações (atraso no desenvolvimento psicomotor, doenças psiquiátricas, entre outras) e da sua flutuação ao longo da vida, permite uma capacidade diagnóstica mais sensível e precoce, com benefícios na qualidade de vida do doente. Concretamente, as manifestações do foro da Imunologia, muito prevalentes nesta síndrome, têm-se provado extremamente díspares de indivíduo para indivíduo, espelho de uma complexa fisiopatologia que se tem vindo a conhecer cada vez mais aprofundadamente. A suspeição clínica deverá motivar a realização de testes genéticos de modo a obter um diagnóstico definitivo, sendo atualmente utilizado como primeira linha o microarray Comparative Genome Hybridization (CGH) que permite analisar todo o genoma e detetar deleções típicas e atípicas.
Neste Trabalho Final de Mestrado, e tendo em conta a clara necessidade de um seguimento multidisciplinar que acompanhe cada indivíduo ao longo da vida, elaborei uma proposta de plano de seguimento assistencial, baseada numa revisão crítica das recomendações internacionais existentes, às quais propus otimizações à luz da evidência publicada em literatura indexada mais recente.
The 22q11.2 deletion syndrome is the most common microdeletion syndrome worldwide, and it encompasses the formerly designated DiGeorge, velocardiofacial syndromes, and all the conditions by sharing a specific genetic cause – a deletion in the long arm of chromosome 22, region 11.2. This anomaly triggers defects in the embryonic development, resulting in a multisystemic clinical presentation with a substantial phenotypic variability, which makes it particularly hard to diagnose. Although cardiac conotruncal malformations, thymic hypoplasia and hypocalcemia constitute the classical triad of this syndrome, there has been a growing knowledge of other possible manifestations (psychomotor development delay, psychiatric conditions, among others) and corresponding modifications throughout life, which allows a more sensitive and earlier diagnosis. Specifically, immunological manifestations, very prevalent amongst these individuals, have continuously proved to vary greatly case-by-case, reflecting the complexity of the physiopathology. Clinical suspicion must prompt genetic testing in order to confirm the diagnosis. The gold-standard nowadays is Comparative Genome Hybridization microarray, which is able to analyze the entire genome as well as identifying typical and atypical deletions. In this paper, and given the clear need of a multidisciplinary follow-up of each patient throughout his or her life, I elaborated a suggestion of a follow-up plan, based on a literature review of the existent international guidelines, to which I have proposed optimizations in the light of the most recently published literature.
The 22q11.2 deletion syndrome is the most common microdeletion syndrome worldwide, and it encompasses the formerly designated DiGeorge, velocardiofacial syndromes, and all the conditions by sharing a specific genetic cause – a deletion in the long arm of chromosome 22, region 11.2. This anomaly triggers defects in the embryonic development, resulting in a multisystemic clinical presentation with a substantial phenotypic variability, which makes it particularly hard to diagnose. Although cardiac conotruncal malformations, thymic hypoplasia and hypocalcemia constitute the classical triad of this syndrome, there has been a growing knowledge of other possible manifestations (psychomotor development delay, psychiatric conditions, among others) and corresponding modifications throughout life, which allows a more sensitive and earlier diagnosis. Specifically, immunological manifestations, very prevalent amongst these individuals, have continuously proved to vary greatly case-by-case, reflecting the complexity of the physiopathology. Clinical suspicion must prompt genetic testing in order to confirm the diagnosis. The gold-standard nowadays is Comparative Genome Hybridization microarray, which is able to analyze the entire genome as well as identifying typical and atypical deletions. In this paper, and given the clear need of a multidisciplinary follow-up of each patient throughout his or her life, I elaborated a suggestion of a follow-up plan, based on a literature review of the existent international guidelines, to which I have proposed optimizations in the light of the most recently published literature.
Description
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2019
Keywords
Síndrome de Deleção 22q11.2 Imunodeficiência Plano de seguimento assistencial Variabilidade fenotípica Cromossomas humanos par 22 Pediatria