What is a PPM1D related disorder?
The protein PPM1Dis encoded by the PPM1D-gene. Mutations in the last part of the PPM1D-gene cause a premature truncation of the protein which results in a shorter protein. Because the protein is shorter than usual, it has an altered function. PPM1D protein is best known for its role in a pathway that restores damage of DNA, but we assume it also has an important rolein the development of the brain.
How is the PPM1D-related mutation inherited?
PPM1D-related intellectual disability is inherited in an autosomal dominant manner, but to date almost all cases result from a de novo mutation in PPM1D. The latter means that neither parent has the mutation but is spontaneously arose in the DNA of their child Thus, most affected individuals represent simplex cases, i.e., a single occurrence in a family. The recurrence risk for future pregnancies is low (probably <1%) but greater than that of the general population because of the possibility of germline mosaicism in one of the parents. Prenatal testing for the same mutation in future pregnancies is possible.
What is the prevalence?
The prevalence is currently unknown, but germline mutations in PPM1D are very rare – only 15 patients have been described in literature so far.
What are the clinical features cause by the PPM1D-related mutations?
PPM1D-related mutations can cause the following clinical features:
- Intellectual disability or developmental delay
- Behavioral problems
- Hypotonia
- Broad based gait
- Sensitivity to sounds
- High pain threshold
- Short stature
- Feeding difficulties
- Periods of fever and vomiting
- Facial features
Not all individuals with a PPM1D-mutation have these symptoms.