Dyggve-Melchior-Clausen Syndrome Caused by a Novel Frameshift Variant in a Japanese Patient.

INTRODUCTION: Dyggve-Melchior-Clausen syndrome (DMC) is a rare autosomal recessive spondyloepimetaphyseal dysplasia characterized by short stature, microcephaly, intellectual disability, and coarse face. This disorder is caused by pathogenic/likely pathogenic variants of the DYM gene which encodes dymeclin.

CASE PRESENTATION: Herein, we report a 60-year-old Japanese man who was born to consanguineous parents. He presented with abdominal distention and rectal prolapse in addition to the common features of DMC. We identified a novel homozygous frameshift variant [c.1670delT, p.(Leu557Argfs*20)] in the DYM gene, which introduces a premature stop codon. Histological analysis revealed disarrangement of actin filaments in cultured fibroblasts.

DISCUSSION: To the best of our knowledge, this is the first Japanese case of DMC with a confirmed variant in the DYM gene. This report provides more information about the geographic distribution and phenotypic spectrum of DMC. Moreover, it presents a novel DYM variant and insights about DMC pathology that may be associated with the disarrangement of actin filaments.