Caracteriza????o cl??nica e molecular de pacientes com hipotireodismo cong??nito de Monte Santo-Bahia-Brasil

O hipotireoidismo cong??nito (HC) ?? uma das doen??as metab??licas mais comuns na inf??ncia, com incid??ncia de HC ?? de 1:3.000 a 1:5.000 nascidos-vivos. Quando prim??rio, o HC caracteriza-se por altos n??veis de TSH podendo ser originado por disormonog??nese, deficiente produ????o hormonal ou decorre de disgenesia tireoidiana, defeito embriol??gico que leva a agenesia, hemiagenesia ou ectopia. Na aus??ncia do tratamento hormonal, o HC leva a grave retardo mental, al??m de outras altera????es cl??nicas. A intera????o do horm??nio TSH com o seu receptor (TSHR) tem importante fun????o biol??gica estimulando o crescimento, diferencia????o e fun????o tireoidiana. Muta????es no gene do TSHR t??m sido identificadas como causa de HC heredit??rio ou cong??nito, mas parecem ser raras. Objetivos: 1) Obter genealogia das fam??lias afetadas para determina????o do padr??o de heran??a, identifica????o de afetados e poss??veis portadores; 2) Descrever as caracter??sticas cl??nica-demogr??ficas dos pacientes com HC; 3) Determinar a distribui????o mutacional no gene do receptor do horm??nio estimulante da tireoide (TSHR) nos afetados; 4) Sugerir a????es de sa??de p??blica e de otimiza????o do aconselhamento gen??tico. Material e M??todos: Foram estudados 12 pacientes provenientes de Monte Santo-BA, sendo oito diagnosticados pela triagem neonatal e quatro diagnosticados tardiamente durante expedi????o ?? cidade. Estes ??ltimos foram identificados durante a coleta dos dados geneal??gicos das fam??lias dos afetados. Todos foram investigados para muta????es no gene do TSHR. Toda a regi??o codificadora do gene foi amplificada atrav??s do DNA gen??mico, seguido de SSCP e sequenciamento. Resultados: ?? ??poca da primeira avalia????o, os pacientes apresentaram n??veis elevados de TSH, confirmando o car??ter prim??rio da doen??a, associados a sinais e sintomas do HC. Observou-se grande heterogeneidade cl??nica entre os pacientes mesmo aqueles com grau de parentesco muito pr??ximo. Nenhuma muta????o patog??nica foi encontrada no gene TSHR. Conclus??o: a an??lise das genealogias permitiu observar a heterogeneidade cl??nica e gen??tica da doen??a. N??o foi encontrada nenhuma muta????o no gene TSHR. O estudo de outros genes poder?? ajudar no esclarecimento do HC na regi??o.Congenital hypothyroidism (CH) is one of the most common metabolic disease in childhood, with an incidence of HC is 1:3,000 to 1:5,000 live births. When primary, CH is characterized by high levels of TSH and may be caused by dyshormonogenesis deficient hormone production, or due to thyroid dysgenesis, embryological defect that leads to agenesis, ectopic or hypoplastic. In the absence of hormonal treatment leads to the CH severe mental retardation and other clinical manifestations. The interaction of stimulanting thyroid growth, differentiation and function. Mutations in the TSHR gene have been identified as a cause of hereditary or congenital CH, but appear to be rare. Objectives: 1) Get genealogy of the affected families to detemine the pattern of inheritance, and possible identification of affected patients; 2) Describe the clinical and demographic characteristics of patients witc CH; 3) Determine the mutational distribution in the TSHR gene in the affected individuals; 4) Suggest public health actions and for genetic counseling optimization. Methods: We studied 12 patients from Monte Santo-Bahia, eight were diagnosed by newborn screening and four diagnosed late during an expedition to the city. The latter were identified during the collection of genealogical data of families those affected. All were investigated for mutations in the TSHR. The entire coding region of the gene was amplified using genomic DNA followed by SSCP and sequencing. Results: At first evaluation, all patients had elevated TSH levels, confirming the primary nature of the disease, associated with signs and/or symptoms of CH. As there was a familial recurrence of the disease, we noticed a large clinical heterogeneity among patients, even those with close family relationship. No pathogenic mutation was found in the TSHR gene. Conclusion: The analysis of pedigrees allowed to observe the clinical and genetic heterogeneity of the disease. We not found mutation in the TSHR. The study of other genes may help in clarifying the CH i the region