A recurrent mutation in tshb gene underlying central congenital hypothyroidism undetectable in neonatal screening / Uma mutação recorrente no gene tshb resultando em hipotireoidismo congênito central não detectável na triagem neonatal

ABSTRACT Objective: To describe the case of a patient with central congenital hypothyroidism (CCH) due to a recurrent mutation in the TSHB gene, as well as to conduct a genetic study of his family. Case description: It is presented a case report of a 5-month-old boy with a delayed diagnosis of isolated CCH in whom the molecular analysis was performed 12 years later and detected a recurrent mutation (c.373delT) in TSHB gene. The parents and sister were carriers of the mutant allele. Comments: The c.373delT mutation has previously been reported in patients from Brazil, Germany, Belgium, United States, Switzerland, Argentina, France, Portugal, United Kingdom and Ireland. In summary, our case and other ones reported in the literature support the theory that this mutation may be a common cause of isolated TSH deficiency. Isolated TSH deficiency is not detected by routine TSH-based neonatal screening, representing a clinical challenge. Therefore, when possible, molecular genetic study is indicated. Identification of affected and carriers allows the diagnosis, treatment and adequate genetic counseling.

RESUMO Objetivo: Descrever o caso de um paciente com hipotireoidismo congênito central (HCC) por conta de uma mutação recorrente no gene TSHB, bem como realizar um estudo genético de sua família. Descrição do caso: Relato de caso de um menino de 5 meses de idade com diagnóstico tardio de HCC isolado, em quem a análise molecular foi realizada 12 anos depois e detectou uma mutação recorrente (c.373delT) no gene TSHB. Os pais e a irmã eram portadores do alelo mutante. Comentários: A mutação c.373delT já foi relatada em pacientes do Brasil, da Alemanha, da Bélgica, dos Estados Uinidos, da Suíça, da Argentina, da França, de Portugal, do Reino Unido e da Irlanda. Em resumo, nosso caso e outros relatados na literatura reforçam a teoria de que essa mutação pode ser uma causa comum de deficiência isolada de TSH. A deficiência isolada de TSH não é detectada na triagem neonatal com base na dosagem de TSH, representando um desafio clínico. Portanto, quando possível, o estudo genético molecular é indicado. A identificação dos afetados e dos portadores permite o diagnóstico, o tratamento e o aconselhamento genético adequado.

A RECURRENT MUTATION IN TSHB GENE UNDERLYING CENTRAL CONGENITAL HYPOTHYROIDISM UNDETECTABLE IN NEONATAL SCREENING.

OBJECTIVE: To describe the case of a patient with central congenital hypothyroidism (CCH) due to a recurrent mutation in the TSHB gene, as well as to conduct a genetic study of his family. CASE DESCRIPTION: It is presented a case report of a 5-month-old boy with a delayed diagnosis of isolated CCH in whom the molecular analysis was performed 12 years later and detected a recurrent mutation (c.373delT) in TSHB gene. The parents and sister were carriers of the mutant allele. COMMENTS: The c.373delT mutation has previously been reported in patients from Brazil, Germany, Belgium, United States, Switzerland, Argentina, France, Portugal, United Kingdom and Ireland. In summary, our case and other ones reported in the literature support the theory that this mutation may be a common cause of isolated TSH deficiency. Isolated TSH deficiency is not detected by routine TSH-based neonatal screening, representing a clinical challenge. Therefore, when possible, molecular genetic study is indicated. Identification of affected and carriers allows the diagnosis, treatment and adequate genetic counseling.