NRXN1-related disorders, attempt to better define clinical assessment

Background NRXN1-related disorders are uncommonly reported. The clinical features of the disorders are wide and heterogeneous mainly consisting of undistinctive facial dysmorphism, mild to severe intellectual and speech delay, epileptic seizures, and motor dysfunction. Defects in NRXN1 gene have been identified in cases diagnosed as Pitt-Hopkins-like-syndrome 2 (PTHLS2; OMIM#614325).Methods Literature review of NRXN1-related disorders was conducted and main clinical features of individuals affected by these disorders were analyzed. In addition, clinical features of individuals labelled with PTHSL2 diagnosis were reported. A comparison between international consensus diagnostic criteria for Pitt-Hopkins syndrome (PTHS) and twins presenting with NRXN1-related disorder and followed by this institution were also presented.Results Our data confirmed that NRXN1-related disorders mainly manifest with undistinctive dysmorphic features and neurological involvement consisting of more or less severe developmental delay/intellectual disability, autistic spectrum disorder, and epilepsy. Relationship between PTHSL2 and NRXN1 remains to be established.Conclusions Our present analysis denoted a heterogeneous and unspecific clinical framework of the NRXN1-related disorders mainly affecting the nervous system for which the clinical diagnosis remains inconclusive without the support of genetic analysis. Further contributions are necessary to better clarify the clinical assessment of PTHSL2.