Prevalence
The PACS1-related syndrome is rare. Its prevalence is unknown, but it was estimated to be 0.2-0.3% out of two studied cohorts (one cohort of individuals with intellectual disability at Baylor College of Medicine and one cohort of individuals from the Deciphering Developmental Disorders Study 2015).
Clinical characteristics
Individuals with PACS1-related syndrome have developmental delay / intellectual disability and recognizable facial dysmorphisms. Congenital anomalies, behavioral problems, epilepsy and oral aversion may also be observed.
Molecular characteristics
A recurrent pathogenic variant was detected, in heterozygosity, in the PACS1 gene – c.607C>T, p.(Arg203Trp) – in almost all individuals described in the literature to date. One individual with a different mutation was described: c.608G>A, p.Arg203Gln.
Genetic Counselling
Since the pathogenic variant occurred de novo in all patients, the recurrence risk in siblings of probands is low, i.e. <1% (although higher than in the general population due to the theoretical possibility of germline mosaicism).
Management
Treatment is symptomatic and multidisciplinary.