Ataxia, tremor, intellectual disability: a case of stxbp1 encephalopathy with a new mutation

STXBP1 gene mutations are among the most common mutations in early-onset epileptic encephalopathies. The clinical spectrum of STXBP1 mutations is not limited to epileptic phenotypes and also includes atypical Rett syndrome and non-syndromic sporadic severe intellectual disability. Tremor, dystonia, choreiform movements, stereotypical head movements and ataxia may also be seen. However, the phenotypical spectrum is not as well-known as the other common SCN1A or CDKL5 gene mutations, making the clinical diagnosis difficult and usually requiring gene panel studies or whole exome sequencing for the diagnosis. We present a 17-year-old male patient whose seizures started at the age of 12 years. The patient could only make limited eye contact, would continuously scream, and also had severe intellectual disability, marked ataxic walking and a very significant coarse tremor. The patient was clinically thought to have STXBP1 encephalopathy due to the presence of severe intellectual disability together with tremor, and ataxia. STXBP1 gene analysis revealed a new c. 9_13delCATTG (pIle4Profs*12) (p.I4Pfs*12) (heterozygous) frameshift mutation. In conclusion, STXBP1 encephalopathy should be considered if severe intellectual disability is accompanied by severe tremor and ataxia in a patient with epileptic and developmental encephalopathy. A normal head circumference supports the diagnosis in such patients.