The syndrome is typically caused by heterozygous germline loss-of-function DICER1 alterations accompanied on the other allele by somatic missense mutations occurring at one of a few mutation hotspots within the sequence encoding the RNase IIIb domain.
Germline pathogenic DICER1 gene variants were identified in all probands and several of their relatives: 64% presented with MNG/thyroidectomy as the phenotypic expression of the syndrome.
Germline pathogenic variants in the DICER1 gene are the underlying cause of the syndrome; variants are typically inherited in an autosomal dominant pattern but may arise de novo in the germline or in a somatic mosaic distribution.