RESUMO
CONTEXT: Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents. OBJECTIVE: To assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients. DESIGN: Retrospective study. METHODS: Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed. RESULTS: Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP. CONCLUSION: This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately.
Assuntos
Puberdade Tardia/diagnóstico , Puberdade Tardia/genética , Adolescente , Estudos de Coortes , Biologia Computacional , Simulação por Computador , Diagnóstico Diferencial , Exoma/genética , Feminino , Testes Genéticos , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hipogonadismo/genética , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sequenciamento do ExomaRESUMO
PURPOSE: To describe the results of posterior conjunctival plication for the treatment of secondary eyelid ptosis after eyelid retraction repair in Graves disease. METHODS: Case series. All patients were evaluated preoperatively by routine eye examination and eyelid measurements including Margin Reflex Distance 1 and levator function. Two eyes of 2 patients who presented with ptosis following eyelid retraction repair were corrected with posterior conjunctival plication. RESULTS: Posterior conjunctival plication for secondary ptosis following eyelid retraction repair was successful in 2 eyelids of 2 patients with Graves disease. Follow up period ranged from 6-10 months over which no sign of recurrent ptosis was observed. CONCLUSIONS: Posterior conjunctival plication is an effective surgical technique for the correction of secondary ptosis following eyelid retraction repair in patients with Graves disease.