A 26-month old male born to non-consanguineous parents without any prenatal complications, had severe retrognathia at birth requiring G-tube placement and mandibular enhancement procedure. He had severe developmental delay with inability to sit, no speech development, severe cognitive issues and seizures developed at 9 months. Examination showed bilateral epicanthic folds with mid-facial hypoplasia, generalized icthyosis and diffuse hypotonia. MRI showed multiple brain malformations including partial agenesis of corpus callosum and diffuse polymicrogyria. A sequencing panel showed two mutations, a homozygous pathogenic frame shifts sequence change in the SNAP29 gene, associated with the CEDNIK syndrome. He has continued to have profound developmental delay and at 2 years is functioning in the 4-6 month range.

Our patient’s DNA analysis of SNAP29 gene demonstrated a homozygous one base pair duplication in exon 2, c.354dup. This pathogenic sequence change results in an amino acid frameshift and creates a premature stop codon 14 amino acids downstream of the mutation, p.Leu119Alafs*15. This pathogenic change is predicted to result in an abnormal transcript, causing truncated SNAP29 protein with abnormal function.

SNAP proteins are t-SNARE proteins that function in intracellular vesicle fusion. SNAP29 has been determined to bind to a broad range of syntaxin fusion proteins and is involved in a number of intracellular transport steps and would impact a variety of neuroectodermal tissues. Recent study suggest that SNAP has additional role as a negative modulator of neurotransmitter release by slowing the recycling of the SNARE-associated fusion machinery and synaptic vesicle turnover. This may be related to the severe neurologic al manifestations shown by patients with CEDNIK syndrome.