Parents

Marbach-Schaaf Synsdrome (MASNS) is an extremely rare neurodevelopmental disorder that was recently described by Dr. Schaaf, Dr. Marbach and colleagues, and has been identified in only around 25 individuals worldwide. The incidence and prevalence of this syndrome is unknown due 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.

Not all individuals with a mutation in the PRKAR1B gene present the same features. MASNS is mainly characterized by global developmental delay with speech delay and behavioral abnormalities including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), movement disorders, such as dyspraxia and apraxia and low sensitivity to pain, among others.

In terms of therapies, it is generally recommended a coordinated multidisciplinary team directed to the symptoms the individual manifests, including physical, occupational and speech therapy.

Inheritance
The inheritance pattern of the disease caused by PRKAR1B mutations is autosomal dominant. Autosomal dominant is a pattern of inheritance characteristic of some genetic disorders. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that a single copy of the mutated gene (from one parent) is enough to cause the disorder. A child of a person affected by an autosomal dominant condition has a 50% chance of being affected by that condition via inheritance of a dominant allele.

Abnormal genes can either be inherited from a parent, or can result from de novo mutations, meaning that the parents are unaffected and the mutation arose spontaneously during the development of the parents’ sperm and egg cells. All MASNS cases reported up to date are de novo mutations.

Many patients carried the same mutation (c.1003C>T, p.Arg335Trp), suggesting a potential mutational hotspot (a segment of DNA that is especially prone to genetic alteration).