RESUMO
Schinzel-Giedion syndrome is a rare autosomal dominant disorder comprising postnatal growth failure, profound developmental delay, seizures, facial dysmorphisms, genitourinary, skeletal, neurological, and cardiac defects. It was recently revealed that Schinzel-Giedion syndrome is caused by de novo mutations in SETBP1, but there are few reports of this syndrome with molecular confirmation. We describe two unrelated Brazilian patients with Schinzel-Giedion syndrome, one of them carrying a novel mutation. We also present a review of clinical manifestations of the syndrome, comparing our cases to patients reported in literature emphasizing the importance of the facial gestalt associated with neurological involvement for diagnostic suspicion of this syndrome.
Assuntos
Anormalidades Múltiplas/genética , Proteínas de Transporte/genética , Anormalidades Craniofaciais/genética , Face/fisiopatologia , Deformidades Congênitas da Mão/genética , Deficiência Intelectual/genética , Unhas Malformadas/genética , Proteínas Nucleares/genética , Anormalidades Múltiplas/fisiopatologia , Brasil , Criança , Anormalidades Craniofaciais/fisiopatologia , Feminino , Deformidades Congênitas da Mão/fisiopatologia , Humanos , Hidronefrose/genética , Hidronefrose/fisiopatologia , Lactente , Deficiência Intelectual/fisiopatologia , Masculino , Mutação , Unhas Malformadas/fisiopatologia , Convulsões/genética , Convulsões/fisiopatologia , Análise de Sequência de DNARESUMO
OBJECTIVES: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. METHODS: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic characterization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed. RESULTS: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-γ production by cluster of differentiation (CD)4+ and CD8+ T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phorbol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8+ and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity. CONCLUSION: Following previous reports in the literature for other conditions, our data showed that patients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.