Main clinical features
Individuals with MASNS have global developmental delay with speech delay and behavioural abnormalities, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).
Affected individuals also show movement disorders, such as dyspraxia and apraxia. Other characteristics are high pain tolerance, sleep disturbances, and variable nonspecific dysmorphic features.
Of note, not all individuals with a mutation in the PRKAR1B gene present all these features.
Prevalence
MASNS is an extremely rare disorder that have been described in only around 25 families worldwide. The incidence and prevalence of this syndrome is unknown owing to the limited number of cases identified so far. It is likely that people with this disorder go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population.
Inheritance
The genetic variants identified in patients with MASNS, which were found by exome sequencing are missense variants in the PRKAR1B gene. The inheritance pattern of the disease caused by PRKAR1B mutations is autosomal dominant and to date, all documented cases are considered de novo mutations. Thus, most affected individuals represent simplex cases, i.e., a single occurrence in a family. The recurrence risk for future pregnancies is low (probably <2%) but greater than that of the general population because of the possibility of germline mosaicism in one of the parents.
Many patients carried the same mutation (c.1003C>T, p.Arg335Trp), suggesting a potential mutational hotspot.