Treatment in a multidisciplinary team is recommended and is directed to the symptoms manifested by the patient.
The long-term follow-up of the patients should be coordinated by a pediatrician with experience in intellectual disability or a developmental pediatrician.
Special attention should be given to:
- early detection of feeding problems
- monitor the developmental progress, with special attention to language
- early recognition of behavior problems
- regularly neurologic evaluation,
- cardiac evaluation for congenital heart disease
- renal evaluation
- evaluation for genital abnormalities (especially in males)
Unfortunately, currently there is no curative treatment available.
The PACS1-related syndrome has an autosomal dominant inheritance pattern.
If the pathogenic variant occurred de novo in the patient (i.e. it was not detected in the parents), the recurrence risk in subsequent pregnancies of the proband’s parents is low (<1%), although it is slightly higher than for other couples in the general population due to the theoretical possibility of germline mosaicism (Figure 3). Prenatal diagnosis is possible, if requested by the parents.
Figure 3: Pedigree showing occurrence of the de novo pathogenic PACS1 variant in the offspring of healthy parents.
A patient with a pathogenic variant in PACS1 has a 50% risk (i.e. a probability of 1 in 2) of transmitting this variant to his/her descendents (Figure 4). So far, this has not been reported.
Figure 4: Pedigree showing occurrence of probability of an affected individual transmitting the pathogenic PACS1 variant in his/her offspring.