Developmental regression and cerebellar atrophy in a patient with congenital fiber-type disproportion and a de novo heterozygous CTBP1 variant

Abstract

  We identified a variant in the carboxyl terminal binding protein 1 gene, NM_001328.3 (CTBP1) : c.1024C＞T [p.R342W] , in a 14-year-old boy who had psychomotor regression and progressive cerebellar atrophy. The CTBP1 is a causative gene of hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (HADDTS ; #617915). This patient showed two characteristics compared with the findings in previously reported cases : 1) initial diagnosis of congenital fiber-type disproportion (CFTD) was made by muscle biopsy at his age of 4 years, and 2) there was no tooth enamel defect, which is one of the main symptoms of HADDTS. Because HADDTS is associated with various central nervous system diseases, CTBP1 should be considered as a possible candidate gene for patients showing a clinically progressive course of psychomotor regression and progressive cerebellar atrophy.