Professionals

Clinical
The phenotype is broad, ranging from severe prenatal/lethal forms with fetal hydrops to milder adult presentations.

•    Most individuals have developmental delay and intellectual disability, sometimes with loss of skills over time.
•    Early low muscle tone often progresses to spasticity and motor impairment, with possible neuropathy and weakness.
•    Behavioral problems (autistic traits, anxiety, ADHD) and seizures are common, whereas some patients develop movement disorders like ataxia, tremor, or dystonia.
•    Many show distinctive facial features similar to Coffin-Lowry syndrome.
•    Additional findings include skeletal abnormalities, eye movement issues, and occasional heart problems.

The milder forms are characterized by mild intellectual disability or even near-normal cognition, with early onset of symptoms but slow progression.

The high incidence of miscarriages in affected families further underscores the gene's critical role in embryonic development.

In most cases, neuroimaging findings such as white matter loss or thinning of the corpus callosum may be evident.

Prevalence
It is an extremely rare condition, with the primary study identifying only 13 individuals from 8 unrelated families.

Inheritance
This neurodevelopmental disorder is caused by bi-allelic variants in the RPS6KC1gene and follows an autosomal recessive inheritance pattern.