Floppy baby syndrome as the first presentation of HADDTS associated with CTBP1 mutation

The CtBP1 protein is a transcriptional regulator that interacts with chromatin-modifying enzymes and modulates gene expression in various cellular pathways. The dominant negative de novo molecular variant c.1024C>T, p.Arg342Trp in the CTBP1 gene is associated with hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (HADDTS). Here we present a male patient with a recurrent hotspot mutation in the CTBP1 gene and a phenotype consistent with HADDTS. The patient presented with global developmental delay, floppy infant syndrome, ataxia, intellectual disability with speech disorder, facial dysmorphia, enamel defect, constipation, and cerebellar atrophy on brain imaging. This is the 18 th reported case of this ultra-rare disorder, and the first patient of Polish origin. Diagnosing neurodevelopmental disorders remains challenging; however, modern large-scale genetic tests and a diagnostic approach from genotype to phenotype enable the diagnosis of an increasing number of patients with rare diseases that present non-specifically but have a severe course.