*2.7.1 Prenatal screening*

In the presence of family history of retinoblastoma and when a specific RB1 mutation is detected, a pregnancy at risk can be tested by chorionic villus sampling or amniocentesis. Prenatal testing and preimplantation genetic diagnosis are indicated as approximately 30% of newborns with an RB1 mutation will harbor a vision-threatening tumor [82, 83].

Amniocentesis can be used to screen the fetus for carrying *RB1* gene using the above-mentioned methods. If an *RB1* pathogenic variant was identified, then fetal ultrasonography may be used to identify intraocular tumor as small as 2–3 mm in size [84]. If tumors are present, preterm delivery to allow early treatment may be indicated. Alternatively, early term delivery (i.e., 36–38 weeks gestation) can be induced even if no intraocular tumor can be detected as this was found to improve the visual outcome and reduce the need for invasive tests and therapies in the postnatal period [83, 85].

Prenatal testing and management may raise several ethical issues especially if it involved termination of pregnancy. A generally accepted approach is to discuss all options with the parents and leave them to decide on further steps.

## *2.7.2 Genetic screening and counseling after birth*

Genetic testing should be performed carefully especially when the propand's blood is found negative for pathogenic mutations. It remains possible that large genetic rearrangement is being missed or they are mosaicism for RB1 mutation.

Carriers of RB1 pathogenic variants should be frequently examined for development of new tumors whether under anesthesia or in the outpatient setting until they reach 9 years of age and the frequency of follow-ups should be reduced thereafter. For relatives who do not carry the mutation, no additional monitoring is required [86]. However, proband's offspring will always be at risk of developing RB and be tested for the RB1 pathogenic mutation identified and proper counseling and clinical monitoring should be implemented. Additionally, all retinoblastoma survivors should have life-long surveillance for other lethal secondary tumors [21, 87, 88].
