De novo pathogenic variants in <i>STXBP1</i> encoding syntaxin1-binding protein (STXBP1, also known as Munc18-1) lead to a range of early-onset neurocognitive conditions, most commonly early infantile epileptic encephalopathy type 4 (EIEE4, also called STXBP1 encephalopathy), a severe form of epilepsy associated with developmental delay/intellectual disability.
These findings suggest that impaired cortico-striatal excitatory transmission is a plausible mechanism that triggers epilepsy in Stxbp1 and Scn2a haplodeficient mice.
Heterozygous de novo mutations in the neuronal protein Munc18-1 are linked to epilepsies, intellectual disability, movement disorders, and neurodegeneration.
Mutations in STXBP1 have been associated with a series of (epileptic) neurodevelopmental disorders collectively referred to as STXBP1-encephalopathy (STXBP1-E).
Mutations in the synaptic machinery gene syntaxin-binding protein 1, STXBP1 (also known as MUNC18-1), are linked to childhood epilepsies and other neurodevelopmental disorders.
FOXG1 syndrome is as an epileptic-dyskinetic encephalopathy whose clinical presentation bears similarities with ARX- and STXBP1-gene related encephalopathies.
STXBP1 gene variants have been identified in patients with many different types of epilepsy, including Dravet syndrome and epileptic encephalopathies, suggesting STX1B plays a similar role.
The patients display common clinical features, including intellectual disability with epilepsy, owing to the presence of STXBP1 within the deletion, nail dysplasia and bone malformations, in particular patellar abnormalities attributed to LMX1B deletion, epistaxis and cutaneous-mucous telangiectasias explained by ENG haploinsufficiency and common facial dysmorphism.
Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies.
We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality.
In conclusion, the case described here suggests a relationship between the Rett syndrome and the STXBP1 gene not described so far, making the search for STXBP1 gene mutations advisable in patients with Rett syndrome and early onset of epilepsy.
Mutations in STXBP1 have first been reported in early onset epileptic encephalopathy with suppression-bursts, then in infantile spasms and, more recently, in patients with non syndromic mental retardation without epilepsy.
STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, has been reported in Ohtahara syndrome, a rare epileptic encephalopathy with suppression burst pattern on EEG, in patients with infantile spasms and in a few patients with nonsyndromic mental retardation without epilepsy.
Our findings suggest that molecular analysis of STXBP1 should be considered for newborns affected by neonatal encephalopathy associated with a peculiar EEG pattern, even in the absence of neonatal epileptic seizures.
Mutations of the syntaxin binding protein 1 (STXBP1) have been associated with severe infantile epileptic encephalopathies (Ohtahara syndrome and West syndrome), but also with moderate to severe cognitive impairment and nonsyndromic epilepsy.
This is the first report of a patient with a truncating mutation in STXBP1 that does not showepilepsy, thus, expanding the clinical spectrum associated with STXBP1 disruption.