Families

Prevalence
The NPTN-related syndrome is rare. Its prevalence is unknown, but it may be estimated to be rare based on the prevalence of potentially pathogenic mutations affecting the gene sequence (https://genomes.sfari.org/gene/ENSG00000156642).

Clinical characteristics
Individuals with NPTN-related syndrome have been diagnosed with autism, developmental delay, intellectual disability. Other neurodevelopmental disorders such as epilepsy, ataxia, and others.

Molecular characteristics
Pathogenic de novovariants identified are nonsense, frameshift, and missense. Whereas nonsense and frameshift variants result in hypofunctional heterozygosity, missense variants alter the molecular structure of the protein product hNp.

Genetic Counselling
Since most identified pathogenic variant occurred de novo, the recurrence risk in siblings of probands is low (although higher than in the general population due to the theoretical possibility of germline mosaicism).

Management
Specific treatment is currently undefined and may depend on validation and further understanding of neuroplastin molecular and cellular functions. Treatment is symptomatic and multidisciplinary.