Mutations in the PPM1D-gene can cause the following main clinical features:
Intellectual disability and developmental delay
All individuals had intellectual disability or developmental delay/learning difficulties. The severity of intellectual disability ranged from mild to severe.
Behavioral features
Most individuals presented with behavioral problems, including sensory integration problems, autism spectrum disorder (ASD), anxiety disorder and attention deficit hyperactivity disorder (ADHD).
Other neurological symptoms
Other neurological symptoms include hypotonia (reduced muscle strength), broad based gait (clumsy, staggering movements with a wide-based gait), sensitivity for sounds and a high pain threshold. Brain MRI was performed in several individuals without any substantial findings.
Growth parameters
Individuals are likely to have a short stature and small hands and feet.
Facial features
Individuals with ID-related PPM1D mutations have some characteristic facial features, such as a broad forehead, upturned nose, broad mouth with thin upper lip, and low-set posteriorly rotated ears.
Visual impairment
Vision problems, such as myopia (nearsightedness), hypermetropia (farsightedness) and strabismus (squint), are seen in the majority of the affected individuals.
Periodic illness
Several individuals suffered from periods of vomiting during childhood. The frequency of these periods was variable, but in some cases occurred several times per month. These periods were sometimes accompanied by fever and improved in some individuals.
Other symptoms
Other symptoms include hyperlordosis and hypoplastic nails.