Floppy baby syndrome as the first presentation of HADDTS associated with CTBP1 mutation
Department of Medical Genetics, The Children’s Memorial Health Institute, Warsaw, Poland
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
Department of Diagnostic Imaging, The Children’s Memorial Health Institute, Warsaw, Poland
Department of Pediatrics, Nutrition, and Metabolic Disorders, The Children’s Memorial Health Institute, Warsaw, Poland
Folia
Neuropathol 2026; 64 (2)
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
18th
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.
Keywords
CTBP1 gene, HADDTS, floppy baby, ataxia, developmental delay
Integrated with
