9.5  Screening of Relatives SOP

9.5.1  Objective

Accurate deployment of resources for early diagnosis or exclusion of hereditary retinoblastoma in relatives of the proband.

9.5.2  Applicability

Primary and specialist caregivers for families of children with bilateral or unilateral retinoblastoma.

9.5.3  Scope

Firstand second-degree child-relatives of a child with bilateral or unilateral retinoblastoma require surveillance for retinoblastoma tumors.

9.5.4  Clinical Significance

When the RB1 gene [9] mutation is identified in the proband, relatives can be molecularly tested for that mutation, so that only carriers require clinical surveillance [10]. Children shown to not carry the family’s RB1 mutant allele avoid further surveillance, EUAs, and clinical examinations. This saves health care dollars and yet provides optimal standard of care [10].

a

BILATERAL proband

Fig. 9.10  When the RB1 mutation(s) are not known for the proband, the risk for their relatives to develop retinoblastoma can be estimated to be high (red), moderate (green), or low (blue). The risk of relatives inheriting the mutant allele depends on the number of intervening “apparently normal” individuals, each of whom has a 10%-chance of carrying but not expressing the mutant allele. The risk therefore falls by a factor of 0.1 for each intervening unaffected generation. (a) All (100%) probands with a family history of retinoblastoma or bilateral tumors have an RB1 mutant allele and a 45% risk of developing retinoblastoma. The risk for the relatives to carry the RB1 mutant allele is shown. (b) Unilateral probands without a family history have a 15% chance to carry a germline RB1 mutant allele. The risk for the relatives to inherit that allele is shown. (c) Infants born with a risk to develop retinoblastoma are examined at regular intervals to detect and treat tumors early to obtain the best visual results. Examination under anesthetic (EUA) (rectangle) and clinical examination with widely dilated pupils (triangle) are performed at the intervals indicated, most frequently for high risk (red, more than 0.2%) and less frequently for medium risk (green, between 0.2 and 0.02%). Low-risk (blue, less than 0.02%) children do not undergo EUA but have regular clinical examinations

•When the family RB1 mutation is not known (Figs. 9.10 and 9.11a):

−−With a positive family history, but no knowledge of the RB1 mutation, each family member is screened until the age of 9 years, according to the empiric risk to develop retinoblastoma (Figs. 9.10 and 9.11a).

•When the family RB1 mutation is known:

−−Early prenatal molecular counseling and testing allows informed family-planning decisions;

perinatal management of affected babies including premature delivery at 35–36 weeks gestation, providing the earliest treatment for potential macular tumors to optimize visual outcome [10] (Fig. 9.3f, g).

−−RB1 mutation carriers are screened closely for early diagnosis of small, easily treated retinoblastoma; relatives proven to not have the family’s RB1 mutation do not require clinical surveillance (Fig. 9.11b).