Phenotypic spectrum associated with pathogenic mutation in the NRG1 gene in Acadian family.

NRG1 is a gene that encodes for a protein that binds to a receptor of the tyrosine kinase family which is essential for the survival of the central nervous system development during embryogenesis. Mutation of the NRG1 gene causes aganglionosis, which leads to Hirschsprung disease. Two brothers of Acadian descent presented with a history of Hirschsprung disease, in association with other anomalies including congenital heart disease, learning difficulties, developmental issues, and hypopigmented hair patch. Molecular analysis in both siblings revealed a heterozygous pathogenic mutation in the NGR1 gene (c.235C>T [p.Arg79*]), that was inherited from an unaffected father. This family expands our knowledge about the phenotypic spectrum associated with pathogenic mutation in the NRG1 gene with intrafamilial variability and the likely reduced penetrance for the phenotypic expression.

Complete reversibility of pembrolizumab-induced eosinophilic fasciitis without corticosteroids: A case report.

Checkpoint inhibitor immunotherapy has recently started to play a fundamental role in the management of metastatic melanoma. It is however accountable for many undesirable adverse effects involving many organ systems. Eosinophilic fasciitis is a rare immune-related adverse effect associated to checkpoint inhibitors such as pembrolizumab and nivolumab. We report the case of a 25-year-old male who received pembrolizumab as a second-line therapy for metastatic melanoma. Approximately 8 months after starting the treatment, the patient developed signs and symptoms of eosinophilic fasciitis, including edema of his hands and lower legs, as well as joint limitation. Pembrolizumab was discontinued after 15 cycles because of symptom progression. The patient experienced complete resolution of symptoms 4 months after cessation of pembrolizumab and without corticosteroids. This case illustrates the reversibility of this immune adverse effect by discontinuation of the treatment, speculating that corticotherapy may not be needed in all cases.